2024/03/15 更新

写真a

ナカイ ナオヤ
中井 直也
NAKAI Naoya
所属
人間文化学研究院
部局
人間文化学部 生活栄養学科
職名
教授
外部リンク

私の一言メッセージ

  • 栄養摂取や運動が骨格筋量の維持・増進に及ぼす影響を個体レベルおよび細胞レベルで研究しています。基礎研究で得た知見を社会へ還元することを目指しています。

学歴

  • 同志社大学   法学部   法律学科

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    国名: 日本国

学位

  • 博士(医学) ( 1997年3月   名古屋大学 )

  • 体育学修士 ( 1993年3月   筑波大学 )

研究キーワード

  • 運動栄養学

経歴

  • 滋賀県立大学   人間文化学部 生活栄養学科   教授

    2015年4月 - 現在

  • 大阪大学   医学系研究科   准教授

    2004年10月 - 2015年3月

所属学協会

  • 日本スポーツ栄養学会

    2015年4月 - 現在

  • 日本アミノ酸学会

    2007年4月 - 現在

  • 日本体力医学会

    1992年4月 - 現在

  • 日本栄養・食糧学会

    1991年5月 - 現在

研究分野

  • ライフサイエンス / スポーツ科学

学会等における役職

  • 日本アミノ酸学会  評議員  その他役職   2022年4月1日 ~ 現在

  • 日本栄養食糧学会  参与  その他役職   2016年4月1日 ~ 現在

  • 日本体力医学会  評議員  その他役職   2013年4月1日 ~ 現在

研究シーズ

  • 骨格筋培養細胞モデルを利用した運動刺激および栄養刺激効果の解析と応用

論文

  • Inhibition of the mitochondrial respiratory chain reduces catecholamine stimulated lipolysis via increasing lactate production in 3T3 L1 adipocytes. 査読

    Mol Med Rep   28 ( 6 )   229   2023年12月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3892/mmr.2023.13116

  • Intermittent fasting reduces mouse body fat while maintaining muscle mass by regulating protein synthesis and autophagy. 査読

    115   112130   2023年11月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.nut.2023.112130

  • Low-carbohydrate, high-fat diet and running exercise influence bone parameters in old mice. 査読 国際誌

    Aikawa Y, Yamashita T, Nakai N, Higashida K.

    J Appl Physiol   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

    DOI: 10.1152/japplphysiol.00789.2021.

  • BDK knockout skeletal muscle satellite cells exhibit enhanced protein translation initiation signal in response to BCAA in vitro. 査読 国際誌

    Nakai N, Iida N, Kitai S, Shimomura Y, Kitaura Y, Higashida K.

    Biosci Biotechnol Biochem.   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

    DOI: 10.1093/bbb/zbac021

  • Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue 査読 国際誌

    Nodoka Takeuchi, Kazuhiko Higashida, Xi Li, Naoya Nakai

    Mol Biol Rep   48 ( 9 )   6269 - 6276   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

    DOI: 10.1007/s11033-021-06617-1

  • Basal and resistance exercise-induced increase in protein synthesis is impaired in skeletal muscle of iron-deficient rats 査読 国際誌

    Kazuhiko Higashida, Sachika Inoue, Nodoka Takeuchi, Satoru Ato, Riki Ogasawara, Naoya Nakai

    Nutrition   91-92   111389   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

    DOI: 10.1016/j.nut.2021.111389

  • Iron deficiency attenuates protein synthesis stimulated by branched-chain amino acids and insulin in myotubes 査読

    Higashida K., Inoue S., Nakai N.

    Biochemical and Biophysical Research Communications   531 ( 2 )   112 - 117   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Biochemical and Biophysical Research Communications  

    Iron deficiency anemia indicates poor nutrition and is a public health problem. Iron deficiency is also associated with muscle weakness. However, the intracellular mechanisms by which iron deficiency induces muscle weakness are obscure. The purpose of the present study was to evaluate the effect of iron deficiency on protein synthesis in basal and branched-amino acids (BCAA)- and insulin-stimulated state in muscle cells. Differentiated C2C12 myotubes were incubated with an iron chelator, deferoxamine mesylate, and then stimulated with BCAA or insulin to activate protein synthesis. This iron deprivation resulted in a significant reduction in the abundance of iron-containing proteins, such as the mitochondrial complex 1 subunit protein, compared to control cells, but not of protein that does not contain iron, such as citrate synthase. Proteins involved in glucose utilization, such as glucose transpoter-1, hexokinase and AMP-activated protein kinase (AMPK), were upregulated under iron deficiency. Additionally, rates of BCAA- and insulin-stimulated protein synthesis, measured by puromycin incorporation, were lower in iron-deficient myotubes than in control cells. We suggest that low iron availability attenuates BCAA- and insulin-stimulated protein synthesis, possibly via activation of AMPK in myotubes. The present findings advance the understanding of the importance of iron to skeletal muscle protein synthesis and, thus, may contribute to the prevention of sarcopenia and frailty.

    DOI: 10.1016/j.bbrc.2020.07.041

    Scopus

    その他リンク: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85089189302&origin=inward

  • Autophagy under glucose starvation enhances protein translation initiation in response to re-addition of glucose in C2C12 myotubes. 査読

    Nakai N, Kitai S, Iida N, Inoue S, Higashida K

    FEBS Open Bio.   10 ( 10 )   2149 - 2156   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

    DOI: 10.1002/2211-5463.12970

  • Induction of autophagy and changes in cellular metabolism in glucose starved C2C12 myotubes. 査読 国際誌

    Nakai N, Kitai S, Iida N, Inoue S, Nakata K, Murakami T, Higashida K.

    J Nutr Sci Vitaminol (Tokyo).   66 ( 1 )   41 - 47   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

  • Iron deficiency attenuates catecholamine stimulated lipolysis via downregulation of lipolysis related proteins and glucose utilization in 3T3 L1 adipocytes. 査読 国際誌

    Higashida K, Takeuchi N, Inoue S, Hashimoto T, Nakai N.

    Mol Med Rep.   21 ( 3 )   1383 - 1389   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

  • Effect of a high fat and high protein diet on exercise-induced skeletal muscle hypertrophy in rats. 査読

    Fujii T, Sonou T, Nakai N, Okamura K

    Int. J. Nutri.   4 ( 3 )   29 - 40   2019年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.14302/issn.2379-7835.ijn-19-3011

  • Low-carbohydrate high-protein diet diminishes the insulin response to glucose load via suppression of SGLT-1 in mice. 査読

    Higashida K, Terada S, Li X, Inoue S, Iida N, Kitai S, Nakai N.

    Biosci Biotechnol Biochem   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/09168451.2018.1533803

  • Leucine supplementation after mechanical stimulation activates protein synthesis via L-type amino acid transporter 1 in vitro. 査読 国際誌

    Nakai N, Kawano F, Murakami T, Nakata K, Higashida K.

    J Cell Biochem.   119 ( 2 )   2094 - 2101   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

    DOI: 10.1002/jcb.26371.

  • Vibration acceleration promotes bone formation in rodent models. 査読 国際誌

    Uchida R, Nakata K, Kawano F, Yonetani Y, Ogasawara I, Nakai N, Mae T, Matsuo T, Tachibana Y, Yokoi H, Yoshikawa H.

    PLoS One.   12 ( 3 )   e0172614   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0172614.

  • Prenatal myonuclei play a crucial role in skeletal muscle hypertrophy in rodents. 査読 国際誌

    Kawano F, Ono Y, Fujita R, Watanabe A, Masuzawa R, Shibata K, Hasegawa S, Nakata K, Nakai N.

    Am J Physiol Cell Physiol.   312 ( 3 )   C233 - C243   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/ajpcell.00151.2016.

  • Muscle-specific deletion of BDK amplifies loss of myofibrillar protein during protein undernutrition. 査読 国際誌

    Ishikawa T, Kitaura Y, Kadota Y, Morishita Y, Ota M, Yamanaka F, Xu M, Ikawa M, Inoue N, Kawano F, Nakai N, Murakami T, Miura S, Hatazawa Y, Kamei Y, Shimomura Y.

    Sci Rep.   7   39825   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep39825.

  • Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells. 査読 国際誌

    Nakai, N., Kawano, F. and Nakata, K.

    Mol. Cell. Biochem.   406 ( 1-2 )   285 - 292   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

  • Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration. 査読 国際誌

    Kawano, F., Nimura, K., Ishino. S. Nakai, N., Nakata, K. and Ohira

    J. Appl. Physiol.   119 ( 10 )   1042 - 1052   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

    DOI: 10.1152/japplphysiol.00289

  • Differences in histone modifications between slow- and fast-twitch muscle of adult rats and following overload, denervation, or valproic acid administration. 査読

    Kawano, F, Nimura, K, Ishino. S, Nakai, N, Nakata, K, Ohira

    J. Appl. Physiol.   119 ( 10 )   1042 - 1052   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1152/japplphysiol.00289

  • Phosphorylation of Hsp25 at serine 15 is promoted in immature fibers following in situ muscle contraction 査読

    Kawano F, Shibaguchi T, Nakai N, Nakata K, Ohira Y

    J Phys Fitness Sports Med   4 ( 2 )   231 - 239   2015年

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    記述言語:日本語   出版者・発行元:The Japanese Society of Physical Fitness and Sports Medicine  

    Heat shock protein 25 (Hsp25) phosphorylation plays a protective role following mechanical stress in skeletal muscle fibers. We previously reported that phosphorylation at serine 15 of Hsp25 (p-Ser15) was enhanced during regrowth of muscle fibers in rats with muscle atrophy due to tail suspension. However, it is still unclear how p-Ser15 contributes to myogenesis and regeneration of skeletal muscle fibers. We performed the present study to investigate p-Ser15 levels at different stages of myogenic differentiation in regenerating soleus muscle fibers of adult rats. Muscle regeneration was induced by muscle injury with intramuscular injection of cardiotoxin into the soleus. On day 14 after injury, p-Ser15-positive cells were noted in the regenerating soleus. The nuclei in small p-Ser15-positive cells contained myogenin, but not Pax7. Most of these cells did not exhibit peripheral localization of dystrophin, indicating that these cells were myotubes or immature fibers. Desmin and actinin were present in all cells and fibers regardless of p-Ser15 expression. Forced contraction by nerve stimulation led to increased phosphorylation at Ser15 in the regenerating soleus, as determined by western blot. Furthermore, elevated p-Ser15 was noted particularly in small cells with cross sectional areas less than 300 µm<sup>2</sup>. These results suggest that small immature fibers are responsive to muscle contraction, and subsequently induce a protective response through the phosphorylation of Hsp25.

    DOI: 10.7600/jpfsm.4.231

    CiNii Books

    その他リンク: https://jlc.jst.go.jp/DN/JLC/20011212629?from=CiNii

  • Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells. 査読

    Nakai, N, Kawano, F, Nakata, K

    Mol. Cell. Biochem.   406 ( 1-2 )   285 - 292   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Speed and/or inclination-dependent mobilization of human leg muscles during walking with a unique exception.

    Ohira, T, H. Okabe, F. Kawano, R. Fujita, T. Ohira, K. Ohira, Y. Oke, N. Nakai, R.R. Roy, V.R. Edgerton, Y. Ohira

    Acta Astronautica   116 ( 116 )   237 - 246   2015年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.actaastro.2015.07.017

  • Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via modulation of gene expressions in infiltrated macrophages. 国際誌

    1840 ( 10 )   3170 - 80   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.bbagen.2014.01.014

    PubMed

  • Anti-interleukin-6 receptor antibody (MR16-1) promotes muscle regeneration via modulation of gene expressions in infiltrated macrophages.

    Fujita, R., Kawano, F., Ohira, T., Nakai, N., Shibaguchi, S., Nishimoto, N. and Ohira, Y.

    Biochem. Biophys. Acta.   1840 ( 10 )   3170 - 3180   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Retardation of C2C12 myoblast cell proliferation by exposure to low-temperature atmospheric plasma. 査読 国際誌

    Nakai, N., Fujita, R., Kawano, F., Takahashi, K., Ohira, T., Shibaguchi, T., Nakata, K. and Ohira, Y.

    J. Physiol. Sci.   64 ( 5 )   365 - 375   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(主担当)  

  • ヒラメ筋のヒストン修飾および遺伝子転写における神経切断に伴う不活動の影響

    河野 史倫, 中井 直也, 大平 充宣

    体力科学   63 ( 1 )   125 - 125   2014年

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    記述言語:日本語   出版者・発行元:The Japanese Society of Physical Fitness and Sports Medicine  

    DOI: 10.7600/jspfsm.63.125

    その他リンク: http://search.jamas.or.jp/link/ui/2014173288

  • Retardation of C2C12 myoblast cell proliferation by exposure to low-temperature atmospheric plasma. 査読

    Nakai, N, Fujita, R, Kawano, F, Takahashi, K, Ohira, T, Shibaguchi, T, Nakata, K, Ohira, Y

    J. Physiol. Sci.   64 ( 5 )   365 - 375   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Evaluation of Gene, Protein and Neurotrophin Expression in the Brain of Mice Exposed to Space Environment for 91 Days

    Daniela Santucci, Fuminori Kawano, Takashi Ohira, Masahiro Terada, Naoya Nakai, Nadia Francia, Enrico Alleva, Luigi Aloe, Toshimasa Ochiai, Ranieri Cancedda, Katsumasa Goto, Yoshinobu Ohira

    PLOS ONE   7 ( 7 )   e40112   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occured only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

    DOI: 10.1371/journal.pone.0040112

    Web of Science

  • The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis 査読

    Maria Angela Masini, Elisabetta Albi, Cristina Barmo, Tommaso Bonfiglio, Lara Bruni, Laura Canesi, Samuela Cataldi, Francesco Curcio, Marta D'Amora, Ivana Ferri, Katsumasa Goto, Fuminori Kawano, Remo Lazzarini, Elisabetta Loreti, Naoya Nakai, Takashi Ohira, Yoshinobu Ohira, Silvio Palmero, Paola Prato, Franco Ricci, Linda Scarabelli, Tsubasa Shibaguchi, Renza Spelat, Felice Strollo, Francesco Saverio Ambesi-Impiombato

    PLOS ONE   7 ( 4 )   e35418   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis. In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10(-7) M and 10(-8) M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains. In testes, immunofluorescent reaction for 3 beta-steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1 beta were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3 beta and 17 beta steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 beta expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. -90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules. Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

    DOI: 10.1371/journal.pone.0035418

    Web of Science

  • Effects of Mechanical Over-Loading on the Properties of Soleus Muscle Fibers, with or without Damage, in Wild Type and Mdx Mice 査読

    Masahiro Terada, Fuminori Kawano, Takashi Ohira, Naoya Nakai, Norihiro Nishimoto, Yoshinobu Ohira

    PLOS ONE   7 ( 4 )   e34557   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Effects of mechanical over-loading on the characteristics of regenerating or normal soleus muscle fibers were studied in dystrophin-deficient (mdx) and wild type (WT) mice. Damage was also induced in WT mice by injection of cardiotoxin (CTX) into soleus muscle. Over-loading was applied for 14 days to the left soleus muscle in mdx and intact and CTX-injected WT mouse muscles by ablation of the distal tendons of plantaris and gastrocnemius muscles. All of the myonuclei in normal muscle of WT mice were distributed at the peripheral region. But, central myonuclei were noted in all fibers of WT mice regenerating from CTX-injection-related injury. Further, many fibers of mdx mice possessed central myonuclei and the distribution of such fibers was increased in response to over-loading, suggesting a shift of myonuclei from peripheral to central region. Approximately 1.4% branched fibers were seen in the intact muscle of mdx mice, although these fibers were not detected in WT mice. The percentage of these fibers in mdx, not in WT, mice was increased by over-loading (similar to 51.2%). The fiber CSA in normal WT mice was increased by over-loading (p&lt;0.05), but not in mdx and CTX-injected WT mice. It was suggested that compensatory hypertrophy is induced in normal muscle fibers of WT mice following functional over-loading. But, it was also indicated that muscle fibers in mdx mice are susceptible to mechanical over-loading and fiber splitting and shift of myonuclei from peripheral to central region are induced.

    DOI: 10.1371/journal.pone.0034557

    Web of Science

  • Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission 査読

    Dorianna Sandona, Jean-Francois Desaphy, Giulia M. Camerino, Elisa Bianchini, Stefano Ciciliot, Daniela Danieli-Betto, Gabriella Dobrowolny, Sandra Furlan, Elena Germinario, Katsumasa Goto, Martina Gutsmann, Fuminori Kawano, Naoya Nakai, Takashi Ohira, Yoshitaka Ohno, Anne Picard, Michele Salanova, Gudrun Schiffl, Dieter Blottner, Antonio Musaro, Yoshinobu Ohira, Romeo Betto, Diana Conte, Stefano Schiaffino

    PLOS ONE   7 ( 3 )   e33232   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

    DOI: 10.1371/journal.pone.0033232

    Web of Science

  • Effects of hindlimb unloading on neurogenesis in the hippocampus of newly weaned rats 査読

    Sachiko Nomura, Katsuya Kami, Fuminori Kawano, Yoshihiko Oke, Naoya Nakai, Takashi Ohira, Ryo Fujita, Masahiro Terada, Kazuhiko Imaizumi, Yoshinobu Ohira

    NEUROSCIENCE LETTERS   509 ( 2 )   76 - 81   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Effects of hindlimb suspension (HS) and ambulation recovery on hippocampal neurogenesis of newly weaned rats were studied by using immunohistochemical techniques. The number of proliferating cell nuclear antigen-positive (PCNA(+)) cells in the subgranular zone (SGZ) markedly decreased during normal growth. However, neither HS nor subsequent recovery caused additional changes in the number of PCNA. cells. The number of doublecortin-positive (DCX+) neurons decreased gradually during normal growth. HS resulted in a further decrease in these neurons. However, DCX+ cell numbers became identical to the levels in age-matched controls after 14 days of recovery. PCNA and DCX-double positive cells in the SGZ were also observed, and their cell numbers were not affected by HS and 14-day ambulation. Thus, HS suppressed the generation of DCX+ neurons without affecting PCNA(+) cells in the SGZ of weaned rats. Taken together, hippocampal neurogenesis in weaned rats was not severely affected by HS while it decreased significantly as they had grown. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2011.12.022

    Web of Science

  • HSP25 can modulate myofibrillar desmin cytoskeleton following the phosphorylation at Ser15 in rat soleus muscle 査読

    Fuminori Kawano, Ryo Fujita, Naoya Nakai, Masahiro Terada, Takashi Ohira, Yoshinobu Ohira

    JOURNAL OF APPLIED PHYSIOLOGY   112 ( 1 )   176 - 186   2012年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Kawano F, Fujita R, Nakai N, Terada M, Ohira T, Ohira Y. HSP25 can modulate myofibrillar desmin cytoskeleton following the phosphorylation at Ser15 in rat soleus muscle. J Appl Physiol 112: 176-186, 2012. First published October 13, 2011; doi:10.1152/japplphysiol.00783.2011.-The main purpose of the present study was to investigate the role(s) of 25-kDa heat shock protein (HSP25) in the regulation and integration of myofibrillar Z-disc structure during down-or upregulation of the size in rat soleus muscle fibers. Hindlimb unloading by tail suspension was performed in adult rats for 7 days, and reloading was allowed for 5 days after the termination of suspension. Interaction of HSP25 and Z-disc proteins, phosphorylation status, distribution, and complex formation of HSP25 were investigated. Non- and single-phosphorylated HSP25s were generally expressed in the cytoplasmic fraction of normal muscle. The level of total HSP25, as well as the phosphorylation ratio, did not change significantly in response to atrophy. Increased expressions of HSP25, phosphorylated at serine 15 (p-Ser15) and dual-phosphorylated form, were noted, when atrophied muscles were reloaded. Myofibrillar HSP25 was also noted in reloaded muscle. Histochemical analysis further indicated the localization of p-Ser15 in the regions with disorganization of Z-disc structure in reloaded muscle fibers. HSP25 formed a large molecular complex in the cytoplasmic fraction of normal muscle, whereas dissociation of free HSP25 with Ser15 phosphorylation was noted in reloaded muscle. The interaction of p-Ser15 with desmin and actinin was detected in Z-discs by proximity ligation assay. Strong interaction between p-Ser15 and desmin, but not actinin, was noted in the disorganized areas. These results indicated that HSP25 contributed to the desmin cytoskeletal organization following the phosphorylation at Ser15 during reloading and regrowing of soleus muscle.

    DOI: 10.1152/japplphysiol.00783.2011

    Web of Science

  • Control of muscle protein synthesis in response to exercise and amino acids.

    Nakai, N., Kawano, F., and Ohira, Y.

    J. Phys. Fitness Sports Med.   1 ( 2 )   297 - 305   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Regulation of soleus muscle properties by mechanical stress and/or neural activity. 査読 国際誌

    Kawano, F., Nakai, N. and Ohira, Y.

    J. Phys. Fitness Sports Med.   1 ( 1 )   29 - 36   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

  • Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

    Santucci D, Kawano F, Ohira T, Terada M, Nakai N, Francia N, Alleva E, Aloe L, Ochiai T, Cancedda R, Goto K, Ohira Y.

    PLoS One   7 ( 7 )   e40112   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

  • HSP25 can modulate myofibrillar desmin cytoskeleton following the phosphorylation at ser15 in rat soleus muscle. 査読

    Kawano, F., Fujita, R., Nakai, N., Terada, M., Ohira, T., and Ohira, Y.

    J. Appl. Physiol.   112   176 - 186   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Effects of hindlimb unloading on neurogenesis in the hippocampus of newly weaned rats. 査読

    Nomura, S., Kami, K., Kawano, F., Oke, Y., Nakai, N., Ohira, T., Fujita, R., Terada, M., Imaizumi, K., and Ohira, Y.

    Neurosci Lett.   509 ( 2 )   76 - 81   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. 査読

    Sandonà D, Desaphy JF, Camerino GM, Bianchini E, Ciciliot S, Danieli-Betto D, Dobrowolny G, Furlan S, Germinario E, Goto K, Gutsmann M, Kawano F, Nakai N, Ohira T, Ohno Y, Picard A, Salanova M, Schiffl G, Blottner D, Musarò A, Ohira Y, Betto R, Conte D, and Schiaffino S.

    Plos One   7 ( 3 )   e33232   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Effects of mechanical over-loading on the properties of soleus muscle fibers, with or without damage, in wild type and mdx mice. 査読

    Terada M, Kawano F, Ohira T, Nakai N, Nishimoto N, and Ohira Y.

    Plos One   7 ( 4 )   e34557   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • The impact of long-term exposure to space environment on adult Mammalian organisms: a study on mouse thyroid and testis. 査読

    Masini MA, Albi E, Barmo C, Bonfiglio T, Bruni L, Canesi L, Cataldi S, Curcio F, D'Amora M, Ferri I, Goto K, Kawano F, Lazzarini R, Loreti E, Nakai N, Ohira T, Ohira Y, Palmero S, Prato P, Ricci F, Scarabelli L, Shibaguchi T, Spelat R, Strollo F, and Ambesi-Impiombato FS

    Plos One   7 ( 4 )   e35418   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • The impact of long-term exposure to space environment on adult Mammalian organisms: a study on mouse thyroid and testis. 査読 国際誌

    Masini MA, Albi E, Barmo C, Bonfiglio T, Bruni L, Canesi L, Cataldi S, Curcio F, D'Amora M, Ferri I, Goto K, Kawano F, Lazzarini R, Loreti E, Nakai N, Ohira T, Ohira Y, Palmero S, Prato P, Ricci F, Scarabelli L, Shibaguchi T, Spelat R, Strollo F, Ambesi-Impiombato FS

    Plos One   7 ( 4 )   e35418   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0035418

    PubMed

  • Regulation of soleus muscle properties by mechanical stress and/or neural activity. 査読

    Kawano, F, Nakai, N, Ohira, Y

    J. Phys. Fitness Sports Med.   1 ( 1 )   29 - 36   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Regulation of soleus muscle properties by mechanical stress and/or neural activity. 査読

    Kawano, F, Nakai, N, Ohira, Y

    J. Phys. Fitness Sports Med.   1 ( 1 )   29 - 36   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • HSP25 can modulate myofibrillar desmin cytoskeleton following the phosphorylation at ser15 in rat soleus muscle. 査読

    Kawano, F, Fujita, R, Nakai, N, Terada, M, Ohira, T, Ohira, Y

    J. Appl. Physiol.   112   176 - 186   2012年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

    Santucci D, Kawano F, Ohira T, Terada M, Nakai N, Francia N, Alleva E, Aloe L, Ochiai T, Cancedda R, Goto K, Ohira Y

    PLoS One   7 ( 7 )   e40112   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Effects of mechanical over-loading on the properties of soleus muscle fibers, with or without damage, in wild type and mdx mice. 査読

    Terada M, Kawano F, Ohira T, Nakai N, Nishimoto N, Ohira Y

    Plos One   7 ( 4 )   e34557   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Control of muscle protein synthesis in response to exercise and amino acids.

    Nakai, N, Kawano, F, Ohira, Y

    J. Phys. Fitness Sports Med.   1 ( 2 )   297 - 305   2012年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Control of muscle protein synthesis in response to exercise and amino acids.

    Nakai, N, Kawano, F, Ohira, Y

    J. Phys. Fitness Sports Med.   1 ( 2 )   297 - 305   2012年

     詳細を見る

    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission. 査読

    Sandonà D, Desaphy JF, Camerino GM, Bianchini E, Ciciliot S, Danieli-Betto D, Dobrowolny G, Furlan S, Germinario E, Goto K, Gutsmann M, Kawano F, Nakai N, Ohira T, Ohno Y, Picard A, Salanova M, Schiffl G, Blottner D, Musarò A, Ohira Y, Betto R, Conte D, Schiaffino S

    Plos One   7 ( 3 )   e33232   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Responses of HSC70 expression in diencephalon to iron deficiency anemia in rats. 査読

    Kawano F, Oke Y, Nomura S, Fujita R, Ohira T, Nakai N, Ohira Y

    The journal of physiological sciences : JPS   61 ( 6 )   445 - 456   2011年11月

  • Region-Specific Responses of Adductor Longus Muscle to Gravitational Load-Dependent Activity in Wistar Hannover Rats

    Takashi Ohira, Masahiro Terada, Fuminori Kawano, Naoya Nakai, Akihiko Ogura, Yoshinobu Ohira

    PLOS ONE   6 ( 6 )   e21044   2011年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Response of adductor longus (AL) muscle to gravitational unloading and reloading was studied. Male Wistar Hannover rats (5-wk old) were hindlimb-unloaded for 16 days with or without 16-day ambulation recovery. The electromyogram (EMG) activity in AL decreased after acute unloading, but that in the rostral region was even elevated during continuous unloading. The EMG levels in the caudal region gradually increased up to 6th day, but decreased again. Approximately 97% of fibers in the caudal region were pure type I at the beginning of experiment. Mean percentage of type I fibers in the rostral region was 61% and that of type I+II and II fiber was 14 and 25%, respectively. The percent type I fibers decreased and de novo appearance of type I+II was noted after unloading. But the fiber phenotype in caudal, not rostral and middle, region was normalized after 16-day ambulation. Pronounced atrophy after unloading and re-growth following ambulation was noted in type I fibers of the caudal region. Sarcomere length in the caudal region was passively shortened during unloading, but that in the rostral region was unchanged or even stretched slightly. Growth-associated increase of myonuclear number seen in the caudal region of control rats was inhibited by unloading. Number of mitotic active satellite cells decreased after unloading only in the caudal region. It was indicated that the responses of fiber properties in AL to unloading and reloading were closely related to the region-specific neural and mechanical activities, being the caudal region more responsive.

    DOI: 10.1371/journal.pone.0021044

    Web of Science

  • Regulation on skeletal muscle protein synthesis by amino acid and resistance exercise.

    Nakai, N.

    J. Exerc. Nutr. Biochem.   15 ( 4 )   153 - 161   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Region-specific responses of adductor longus muscle to gravitational load-dependent activity in Wistar Hannover rats.

    Ohira, T., Terada, M., Kawano, F., Nakai, N., Ogura, A., and Ohira, Y.

    PLos One   6 ( 6 )   e21044   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   参加形態:共同(副担当)  

  • Modulation of hippocampal proteins by exposure to simulated microgravity environment during the postnatal development in rats 査読

    Oke Y, Kawano F, Nomura S, Ohira T, Fujita R, Terada M, Shibaguchi T, Nakai N, Ohira Y

    Jpn J Aerospace Environ Med   48 ( 3 )   23 - 34   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Scopus

  • Regulation on skeletal muscle protein synthesis by amino acid and resistance exercise.

    Nakai, N

    J. Exerc. Nutr. Biochem.   15 ( 4 )   153 - 161   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  • Role(s) of mechanical load and satellite cells in the regulation of the size of soleus muscle fibers in rats 査読

    Ohira, Y, Kawano, F, Wang, X.D, Nakai, N, Ohira, T, Okabe, H, Naito, H, Goto, K

    Biological Sciences in Space   24 ( 3 )   135 - 144   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:日本宇宙生物科学会  

    CiNii Books

    その他リンク: http://search.jamas.or.jp/link/ui/2011337789

  • Mechanical stretch induces activation of eukaryotic elongation factor 2 in C2C12 myoblast 査読

    Nakai Naoya, Kawano Fuminori, Oke Yoshihiko, Nomura Sachiko, Terada Masahiro, Ohira Takashi, Ohira Yoshinobu

    FASEB JOURNAL   23   2009年4月

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  • Responses of protein expression in rat brain to deafferentation 査読

    Kawano Fuminori, Nakajima Yoshie, Nakai Naoya, Terada Masahiro, Ohira Takashi, Oke Yoshihiko, Nomura Sachiko, Ohira Yoshinobu

    FASEB JOURNAL   23   2009年4月

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  • DECREASED MUSCLE SENSORY FEEDBACK INFLUENCES THE PROTEIN EXPRESSION IN RAT BRAIN 査読

    Kawano Fuminori, Nakajima Yoshie, Nakai Naoya, Terada Masahiro, Ohira Takashi, Oke Yoshihiko, Nomura Sachiko, Ohira Yoshinobu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   221   2009年

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  • REGION-SPECIFIC RESPONSES OF ADDUCTOR LONGUS MUSCLE TO UNLOADING AND RELOADING IN WISTAR HANNOVER RATS 査読

    Ohira Takashi, Terada Masahiro, Kawano Fuminori, Nakai Naoya, Ochiai Toshimasa, Gyotoku Jun-ichiro, Sudoh Masamichi, Ohira Yoshinobu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   216   2009年

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  • PROTEIN TRANSLATION INITIATION IS ACTIVATED BY MECHANICAL STRETCH IN C2C12 MYOBLAST 査読

    Nakai Naoya, Kawano Fuminori, Oke Yoshihiko, Nomura Sachiko, Terada Masahiro, Ohira Takashi, Ohira Yoshinobu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   206   2009年

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  • HINDLIMB SUSPENSION IMPAIRS HIPPOCAMPAL NEUROGENESIS IN WEANED RATS 査読

    Nomura Sachiko, Kami Katsuya, Kawano Fuminori, Oke Yoshihiko, Nakai Naoya, Terada Masahiro, Ohira Takashi, Imaizumi Kazuhiko, Ohira Yoshinobu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   222   2009年

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  • EFFECT OF HINDLIMB SUSPENSION ON LEARNING CAPACITY IN JUVENILE RATS 査読

    Oke Yoshihiko, Kawano Fuminori, Ohira Takashi, Nomura Sachiko, Terada Masahiro, Nakai Naoya, Ohira Yoshinobu

    JOURNAL OF PHYSIOLOGICAL SCIENCES   59   222   2009年

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  • Effects of mechanical and/or neural stimulation on the properties of soleus muscle fibers in mdx mice 査読

    Lan YB, Terada M, Higo Y, Kawano F, Matsuoka Y, Wang XD, Nakai N, Ohira Y

    Japanese Journal of Aerospace & Environmental Medicine   44   19-29   2007年

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    掲載種別:研究論文(学術雑誌)  

  • Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse. 査読

    Tanaka M, Hayashida Y, Nakao N, Nakai N, Nakashima K

    Biochimica et biophysica acta   1522 ( 1 )   62 - 65   2001年11月

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  • Dietary maltitol decreases the incidence of 1,2-dimethylhydrazine- induced cecum and proximal colon tumors in rats

    Midoriko Tsukamura, Hidemi Goto, Tomiyasu Arisawa, Tetsuo Hayakawa, Naoya Nakai, Taro Murakami, Noriaki Fujitsuka, Yoshiharu Shimomura

    Journal of Nutrition   128 ( 3 )   536 - 540   1998年3月

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    掲載種別:研究論文(学術雑誌)  

    Maltitol is fermented in the colon due to only partial hydrolysis in the small intestine. In the present study, we examined effects of dietary maltitol on dimethylhydrazine-induced intestinal tumor in rats. In experiment 1, rats were fed a fiber-free diet or diets supplemented with 1 or 5 g/100 g maltitol for 27 wk. Each group of rats was injected with dimethylhydrazine or vehicle alone for the first 14 wk of the experimental period. Maltitol supplementation at 1 g/100 g of the diet significantly reduced tumor incidence in the cecum and the 5% supplement reduced tumor incidence in both the cecum and proximal colon in dimethylhydrazine-treated rats. In experiment 2, we investigated the effect of the 1 g/100 g maltitol diet on the short chain fatty acid concentrations in cecal contents of placebo and dimethylhydrazine-treated rats. Intake of the 1 g/100 g maltitol diet doubled (P < 0.05) the concentration of butyrate but did not affect acetate or propionate in the cecal contents. These results suggest that dietary maltitol has a protective effect against dimethylhydrazine-induced tumors in rat cecum and proximal colon and that butyrate produced by bacterial fermentation of maltitol in the cecum may be involved in the protection.

    DOI: 10.1093/jn/128.3.536

    Scopus

    PubMed

  • Effects of aging on the activities of pyruvate dehydrogenase complex and its kinase in rat heart 査読

    N Nakai, Y Sato, Y Oshida, A Yoshimura, N Fujitsuka, S Sugiyama, Y Shimomura

    LIFE SCIENCES   60 ( 25 )   2309 - 2314   1997年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Effects of aging on the activities of heart pyruvate dehydrogenase complex and pyruvate dehydrogenase kinase were examined using 7, 35 and 60 wk old rats. Aging did not affect the total activity of pyruvate dehydrogenase complex but decreased the activity state (percentage of active form) of the complex in rats under the fed condition(52%, 36% and 26% for 7, 35 and 60 wk old rats, respectively). This decrease in the complex activity with aging was suggested to be associated with an age-related decrease in the brood glucose disposal. Starvation for 24 h decreased the activity state to less than 3% in all of the age groups. The activity of pyruvate dehydrogenase kinase associated with the complex was not related to the alteration in the activity state of the complex; the kinase activity was slightly lower in 60 wk old rats than in the younger rats under the fed condition and activation of the kinase by starvation was greater in the younger rats. The mechanism for the decrease in activity of pyruvate dehydrogenase complex was discussed on the basis of glucose and fatty acid utilization of heart muscle cells.

    Web of Science

  • Gender difference in regulation of the branched-chain a-keto acid dehydrogenase complex (bckdc) and its kinase

    R. Kobayashi, Y. Shimomura, T. Murakami, N. Nakai, M. Otsuka, X. Arakawa, K. M. Popov, R. A. Harris

    FASEB Journal   11 ( 9 )   1997年

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    掲載種別:研究論文(学術雑誌)  

    Regulation of the activity state of the hepatic BCKDC during the light-dark cycle differs markedly in male and female rats. Male rats show little evidence of a diurnal rhythm in the regulation of the complex. However, female rats exhibit a profound diurnal rhythm in the activity state. Regardless of gender most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats al the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Changes in blood levels of branched-chain o-keto acids, only known regulators of BCKDH kinase, did not correlate with changes in BCKDC activity state in female rats. Rather it appears that the greater BCKDC phosphorylation is due to a stable increase in BCKDH kinase activity. Western blot analysis indicates that the increased expression of BCKDH kinase protein is responsible for the increase in BCKDH kinase activity. Thus, this study provides evidence for a gender-specific difference in the regulation of branched chain amino acid <atul>olisni. A diurnal variation in expression of BCKDH kinase appears to be ;in important factor in the difference in the regulation of BCKDC1 activity between male and female rats.

    Scopus

  • Activities of liver pyruvate dehydrogenase complex and 3-hydroxyacyl-CoA dehydrogenase in sand rat (Psammomys obesus) 査読

    N Nakai, GR Collier, Y Sato, Y Oshida, N Fujitsuka, Y Shimomura

    LIFE SCIENCES   60 ( 1 )   51 - 55   1996年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The sand rat (Psammomys obesus) is an animal model for non-insulin dependent diabetes mellitus, which is induced by a regular chow diet. The total activity of liver pyruvate dehydrogenase complex in the sand rats under normoglycemic and normoinsulinemic conditions was one half as high as that in the albino rats, but the activity of liver 3-hydroxyacyl-CoA dehydrogenase was more than 4 times greater in the former than in the latter, suggesting a low capacity for glucose oxidation and a high capacity for fatty acid oxidation in the sand rats. These metabolic conditions may be related to the predisposition of the animals towards diabetes. Diet-induced diabetes in the sand rats resulted in decreasing the active form of liver pyruvate dehydrogenase complex and in increasing the activity of liver 3-hydroxyacyl-CoA dehydrogenase, suggesting that the diabetic conditions further suppress glucose oxidation and promote fatty acid oxidation.

    Web of Science

  • Glycogen depletion of the intrafusal fibers in a mouse muscle spindle during prolonged swimming 査読

    A Yoshimura, Y Shimomura, T Murakami, M Ichikawa, N Nakai, C Fujitsuka, M Kanematsu, N Fujitsuka

    AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY   271 ( 2 )   R398 - R408   1996年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    This study investigated the recruitment of different types of intrafusal fibers during prolonged swimming at 60-75% of VO2max mie used 56 male adult mice and examined depletion of glycogen in soleus (Sol) and extensor digitorum longus (EDL) muscle spindles by visual inspection and a newly developed optical scanning method. More than 80% of all spindles from six mice consisted of four fibers: one type I nuclear bag (bag(1)) fiber, one type II nuclear bag (bag(2)) fiber, and two nuclear chain fibers. Glycogen content was estimated in muscle numbers from groups of six mice that had rested or swum for either 0.5, 1, 2, 4, or 8 h. The optical scanning intensity of periodic acid Schiff (PAS)-stained sections was correlated with their biochemically determined glycogen content (r = 0.93). Both methods showed fundamentally the same result: each type of intrafusal fiber has its own typical recruitment pattern during exercise. In the initial phase (0-0.5 h), glycogen depletion was largest in nuclear bag(1) fibers and insignificant in the bag(2) and chain fibers. With the bag(1) fibers having become fatigued, nuclear bag(2) fibers mainly took over during the middle phase (2-4 h). During the last phase (4-8 h), only the glycogen content of chain fibers decreased significantly (4-8 h). There were significant correlations between the recruitment pattern of bag(1) and extrafusal type I fibers in both Sol and EDL, between nuclear bag(2) and type IIa fibers in Sol, and between nuclear chain and type IIb fibers in EDL. This suggests that, during moderately intense exercise, glycogen depletion occurs first in the slow, then the intermediate, and, finally, the fast intrafusal fibers.

    Web of Science

  • Exercise training prevents maturation-induced decrease in insulin sensitivity 査読

    N Nakai, Y Shimomura, N Ohsaki, J Sato, Y Oshida, Ohsawa, I, N Fujitsuka, Y Sato

    JOURNAL OF APPLIED PHYSIOLOGY   80 ( 6 )   1963 - 1967   1996年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    We examined the effects of exercise training initiated before maturation or after maturation on insulin sensitivity and glucose transporter GLUT-4 content in membrane fractions of skeletal muscle. Female Wistar rats (4 wk of age) were divided into sedentary and exercise-trained groups. At 12 wk of age, a subset of the trained animals (Tr) was killed along with a subset of sedentary controls (Sed). One-half of the remaining sedentary animals remained sedentary (Sed-Sed) while the other half began exercise training (Sed-Tr). The remaining rats in the original trained group continued to train (Tr-Tr). Euglycemic clamp (insulin infusion rate at 6 mU . kg body wt(-1) . min(-1)) was performed at 4, 12, and 27 wk. After euglycemic clamp in all animals except the 4-wk-old, hindlimb (gastrocnemius and part of quadriceps) muscles were removed for preparation of membrane fractions. In sedentary rats, glucose infusion rate (GIR) during euglycemic clamp was decreased from 15.9 mg . kg(-1) . min(-1) at 4 wk of age to 9.8 mg . kg(-1) . min(-1) at 12 wk of age and 9.1 mg . kg(-1) . min(-1) at 27 wk of age. In exercise-trained rats, the GIR was not significantly decreased by maturation (at 12 wk) and further aging (at 27 wk). Initiation of exercise after maturation restored the GIR at 27 wk of age to the same levels as these for the corresponding exercise-trained rats. GLUT-4 content in plasma and intracellular membrane fractions of hindlimb muscle obtained just after euglycemic clamp showed the same trend as the results of GIR. These results suggest that exercise training prevented the maturation-induced decrease in insulin sensitivity. Improvement of insulin sensitivity caused by exercise training was attributed, at least in part, to the increase in insulin-sensitive GLUT-4 on the plasma membrane in skeletal muscle.

    Web of Science

  • ENZYMATIC AND GENETIC ADAPTATION OF SOLEUS MUSCLE MITOCHONDRIA TO PHYSICAL-TRAINING IN RATS 査読

    T MURAKAMI, Y SHIMOMURA, N FUJITSUKA, N NAKAI, S SUGIYAMA, T OZAWA, M SOKABE, S HORAI, K TOKUYAMA, M SUZUKI

    AMERICAN JOURNAL OF PHYSIOLOGY   267 ( 3 )   E388 - E395   1994年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    To evaluate the effects of physical training on mitochondrial gene expression and mitochondrial biogenesis in slow-twitch muscle, adult female Sprague-Dawley rats were trained for 3, 6, and 12 wk by running on a motor-driven treadmill (speed of 25 m/min and duration of 90 min/day, 5 days/wk), and the activities of citrate synthase, ubiquinol-cytochrome-c oxidoreductase, cytochrome oxidase, mitochondrial cytochrome b mRNA (by Northern blot analysis), and mitochondrial DNA (by slot-blot and Southern blot analyses) were measured in rat soleus muscle. A DNA probe for detection of mitochondrial mRNA and DNA was prepared from a 1,500-bp fragment of human mitochondrial DNA that included the coding region of the cytochrome b gene. Training for 3, 6, and 12 wk significantly increased the activities of citrate synthase (31, 28, and 47%, respectively), ubiquinol-cytochrome-c oxidoreductase (61, 63, and 77%, respectively), and cytochrome oxidase (25, 26, and 32%, respectively) in muscle. The concentration of cytochrome b mRNA in the muscle was proportionally elevated with the enzyme activities. On the other hand, the mitochondrial DNA concentration in the muscle was not altered by training for 3 or 6 wk but increased significantly after training for 12 wk (35% in the slot-blot analysis and 31% in the Southern blot analysis). These results suggest that an increase in the oxidative capacity of slow-twitch muscle by the relatively short-term training is regulated at the pretranslational step in mitochondrial protein synthesis but that the increase by the long-term training involves mitochondrial replication.

    Web of Science

  • Enzymatic and genetic adaptation of soleus muscle mitochondria to physical training in rats

    T. Murakami, Y. Shimomura, N. Fujitsuka, N. Nakai, S. Sugiyama, T. Ozawa, M. Sokabe, S. Horai, K. Tokuyama, M. Suzuki

    American Journal of Physiology - Endocrinology and Metabolism   267 ( 3 30-3 )   1994年

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    掲載種別:研究論文(学術雑誌)  

    To evaluate the effects of physical training on mitochondrial gene expression and mitochondrial biogenesis in slow-twitch muscle, adult female Sprague-Dawley rats were trained for 3, 6, and 12 wk by running on a motor- driven treadmill (speed of 25 m/min and duration of 90 min/day, 5 days/wk), and the activities of citrate synthase, ubiquinol-cytochrome-c oxidoreductase, cytochrome oxidase, mitochondrial cytochrome b mRNA (by Northern blot analysis), and mitochondrial DNA (by slot-blot and Southern blot analyses) were measured in rat soleus muscle. A DNA probe for detection of mitochondrial mRNA and DNA was prepared from a 1,500-bp fragment of human mitochondrial DNA that included the coding region of the cytochrome b gene. Training for 3, 6, and 12 wk significantly increased the activities of citrate synthase (31, 28, and 47%, respectively), ubiquinol-cytochrome-c oxidoreductase (61, 63, and 77%, respectively), and cytochrome oxidase (25, 26, and 32%, respectively) in muscle. The concentration of cytochrome b mRNA in the muscle was proportionally elevated with the enzyme activities. On the other hand, the mitochondrial DNA concentration in the muscle was not altered by training for 3 or 6 wk but increased significantly after training for 12 wk (35% in the slot-blot analysis and 31% in the Southern blot analysis). These results suggest that an increase in the oxidative capacity of slow- twitch muscle by the relatively short-term training is regulated at the pretranslational step in mitochondrial protein synthesis but that the increase by the long-term training involves mitochondrial replication.

    DOI: 10.1152/ajpendo.1994.267.3.e388

    Scopus

    PubMed

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書籍等出版物

  • 栄養科学イラストレイテッド 運動生理学

    麻見直美,川中健太郎編 他( 担当: 分担執筆)

    羊土社  2019年4月  ( ISBN:978-4-7581-1356-4

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    総ページ数:221   担当ページ:114-130   記述言語:日本語   著書種別:教科書・概説・概論

  • フィットネスインストラクターテキスト

    建帛社  1998年 

  • 健康運動科学(実技編)

    さかた出版  1997年 

  • YMCAスタデイシリーズ13 日本YMCAフィットネスインストラクター教本

    日本YMCA同盟出版部 社会体育インストラクター 資格審査委員会編  1995年 

MISC

  • メカニカルストレスはロイシンによるタンパク質合成促進作用を増強する

    中井 直也, 河野 史倫, 中田 研

    日本栄養・食糧学会大会講演要旨集   68回   266 - 266   2014年4月

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    記述言語:日本語   出版者・発行元:(公社)日本栄養・食糧学会  

  • 2020東京オリンピック・パラリンピックへの架け橋 スポーツ整形外科の果たす役割と夢 スポーツトレーニングと運動器の健康増進

    中田 研, 前 達雄, 米谷 泰一, 中井 直也, 河野 史倫, 吉川 秀樹

    日本整形外科学会雑誌   88 ( 3 )   S900 - S900   2014年3月

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    記述言語:日本語   出版者・発行元:(公社)日本整形外科学会  

  • Differential responses of soleus and plantaris muscle fibers to overloading

    Kawano, Fuminori, Nakai, Naoya, Ohira, Yoshinobu, Ohira, Yoshinobu, Shibaguchi, Tsubasa, Ohira, Takashi

    European Space Agency, (Special Publication) ESA SP   706 SP   2013年

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  • 健康の維持・増進を目指した運動処方のヒトおよびラットにおける再検討

    大平 充宣, 中井 直也, 岡部 洋興

    デサントスポ-ツ科学   32   11 - 18   2011年6月

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    記述言語:日本語   出版者・発行元:石本記念デサントスポ-ツ科学振興財団事務局  

    CiNii Books

  • Effects of Creatine and Its Analog, beta-Guanidinopropionic Acid, on the Differentiation of and Nucleoli in Myoblasts

    Yoshinobu Ohira, Yoshikazu Matsuoka, Fuminori Kawano, Akihiko Ogura, Yoko Higo, Takashi Ohira, Masahiro Terada, Yoshihiko Oke, Naoya Nakai

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   75 ( 6 )   1085 - 1089   2011年6月

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    The effects of supplementation with creatine (Cr) and its analog, beta-guanidinopropionic acid (beta-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4d. Then Cr (1 mM) or beta-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and beta-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the beta-GPA group. Supplementation with beta-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas beta-GPA increased nucleolar sizes in the myotubes. These results suggest that beta-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.

    DOI: 10.1271/bbb.100901

    Web of Science

  • Effects of creatine and its analogue, β-guanidinopropionic acid on the differentiation and nucleoli in myoblasts.

    Biosci. Biotechnol. Biochem.   75 ( 6 )   1085 - 1089   2011年6月

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    記述言語:英語  

    DOI: 10.1271/bbb.100901

    Web of Science

  • 3ケ月の宇宙基地滞在がマウスの生理学的特性に及ぼす影響:宇宙実験のコントロールとしての地上シミュレーション実験

    大平充宣, 中井直也, 河野史倫, 大平宇志, 芝口翼, 藤田諒, 後藤勝正, 石原昭彦, 大石康晴, 山崎将生, 向井千秋, 寺田昌弘, 山下雅道, 宇佐美眞一, 奥野誠, 落合俊昌, 行徳淳一郎

    宇宙利用シンポジウム   27th   122 - 123   2011年3月

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    記述言語:日本語  

    J-GLOBAL

  • メカニカルストレスによるタンパク質合成促進作用におけるphospholipase Cの役割

    中井直也, 河野史倫, 芝口翼, 大平充宣

    体力科学   60 ( 6 )   2011年

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  • Mechanical stretch activates signaling events for protein translation initiation and elongation in C2C12 myoblasts

    Naoya Nakai, Fuminori Kawano, Yoshihiko Oke, Sachiko Nomura, Takashi Ohira, Ryo Fujita, Yoshinobu Ohira

    MOLECULES AND CELLS   30 ( 6 )   513 - 518   2010年12月

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    記述言語:英語   出版者・発行元:KOREAN SOC MOLECULAR & CELLULAR BIOLOGY  

    It has been proposed that mechanically induced tension is the critical factor in the induction of muscle hypertrophy. However, the molecular mechanisms involved in this process are still under investigation. In the present study, the effect of mechanical stretch on intracellular signaling for protein translation initiation and elongation was studied in C2C12 myoblasts. Cells were grown on a silicone elastomer chamber and subjected to 30-min of 5 or 15% constant static or cyclic (60 cycles/min) uniaxial stretch. Western blot analyses revealed that p70 S6 kinase (p70S6K) and eukaryotic elongation factor 2 (eEF2), which are the markers for translation initiation and peptide chain elongation, respectively, were activated by both static and cyclic stretch. The magnitude of activation was greater in response to the 15% cyclic stretch. Cyclic stretch also increased the phosphorylation of MAP kinases (p38 MAPK, ERK1/2 and JNK). However, the pharmacological inhibition of MAP kinases did not block the stretch-induced activation of p70S6K and eEF2. An inhibitor of the mammalian target of rapamycin (mTOR) blocked the stretch-induced phosphorylation of p70S6K but did not affect the eEF2 activation. A broad-range tyrosine kinase inhibitor, genistein, blocked the stretch-induced activation of p70S6K and eEF2, whereas Src tyrosine kinase and Janus kinase (JAK) inhibitors did not. These results suggest that the stretch-induced activation of protein translation initiation and elongation in mouse myoblast cell lines is mediated by tyrosine kinase(s), except for Src kinase or JAK.

    DOI: 10.1007/s10059-010-0147-3

    Web of Science

  • Tyrosine phosphorylation regulates mechanical stretch-induced activation of protein translation initiation in C2C12 myoblasts

    Naoya Nakai, Fuminori Kawano, Yoshihiko Oke, Sachiko Nomura, Takashi Ohira, Ryo Fujita, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effect of antigravity muscle activity on learning capacity and hippocampal protein expression in juvenile rats

    Yoshihiko Oke, Fuminori Kawano, Sachiko Nomura, Takashi Ohira, Ryo Fujita, Naoya Nakai, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effects of IL-6 receptor inhibition and/or heat treatment on the regeneration of injured mouse skeletal muscle

    Ryo Fujita, Takashi Ohira, Katsuya Kami, Yoshihiko Oke, Sachiko Nomura, Fuminori Kawano, Naoya Nakai, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effects of chronic iron deficiency anemia on the protein expression of rat thalamus

    Fuminori Kawano, Yoshihiko Oke, Naoya Nakai, Takashi Ohira, Sachiko Nomura, Ryo Fujita, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effect of hindlimb suspension on hippocampal neurogenesis in weaned rats

    Sachiko Nomura, Katsuya Kami, Fuminori Kawano, Yoshihiko Oke, Takashi Ohira, Ryo Fujita, Naoya Nakai, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Reconsideration of exercise prescription as the countermeasure for prevention of muscle atrophy in space

    Takashi Ohira, Hirooki Okabe, Fuminori Kawano, Yoshihiko Oke, Ryo Fujita, Sachiko Nomura, Naoya Nakai, Tomotaka Ohira, Kazutaka Ohira, Yoshinobu Ohira

    FASEB JOURNAL   24   2010年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers

    Fuminori Kawano, Katsumasa Goto, Xiao Dong Wang, Masahiro Terada, Takashi Ohira, Naoya Nakai, Toshitada Yoshioka, Yoshinobu Ohira

    JOURNAL OF APPLIED PHYSIOLOGY   108 ( 3 )   676 - 685   2010年3月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Kawano F, Goto K, Wang XD, Terada M, Ohira T, Nakai N, Yoshioka T, Ohira Y. Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers. J Appl Physiol 108: 676-685, 2010. First published January 7, 2010; doi: 10.1152/japplphysiol.00478.2009.-Effects of gravitational loading or unloading on the gain of the characteristics in soleus muscle fibers were studied in rats. The tail suspension was performed in newborn rats from postnatal day 4 to month 3, and the reloading was allowed for 3 mo in some rats. Single expression of type I myosin heavy chain (MHC) was observed in similar to 82% of fibers in 3-mo-old controls, but the fibers expressing multiple MHC isoforms were noted in the unloaded rats. Although 97% of fibers in 3-mo-old controls had a single neuromuscular junction at the central region of fiber, fibers with multiple nerve endplates were seen in the unloaded group. Faster contraction speed and lower maximal tension development, even after normalization with fiber size, were observed in the unloaded pure type I MHC fibers. These parameters generally returned to the age-matched control levels after reloading. It was suggested that antigravity-related tonic activity plays an important role in the gain of single neural innervation and of slow contractile properties and phenotype in soleus muscle fibers.

    DOI: 10.1152/japplphysiol.00478.2009

    Web of Science

  • Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers

    Fuminori Kawano, Katsumasa Goto, Xiao Dong Wang, Masahiro Terada, Takashi Ohira, Naoya Nakai, Toshitada Yoshioka, Yoshinobu Ohira

    JOURNAL OF APPLIED PHYSIOLOGY   108 ( 3 )   676 - 685   2010年3月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Kawano F, Goto K, Wang XD, Terada M, Ohira T, Nakai N, Yoshioka T, Ohira Y. Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers. J Appl Physiol 108: 676-685, 2010. First published January 7, 2010; doi: 10.1152/japplphysiol.00478.2009.-Effects of gravitational loading or unloading on the gain of the characteristics in soleus muscle fibers were studied in rats. The tail suspension was performed in newborn rats from postnatal day 4 to month 3, and the reloading was allowed for 3 mo in some rats. Single expression of type I myosin heavy chain (MHC) was observed in similar to 82% of fibers in 3-mo-old controls, but the fibers expressing multiple MHC isoforms were noted in the unloaded rats. Although 97% of fibers in 3-mo-old controls had a single neuromuscular junction at the central region of fiber, fibers with multiple nerve endplates were seen in the unloaded group. Faster contraction speed and lower maximal tension development, even after normalization with fiber size, were observed in the unloaded pure type I MHC fibers. These parameters generally returned to the age-matched control levels after reloading. It was suggested that antigravity-related tonic activity plays an important role in the gain of single neural innervation and of slow contractile properties and phenotype in soleus muscle fibers.

    DOI: 10.1152/japplphysiol.00478.2009

    Web of Science

  • Mechanical stretch activates signaling events for protein translation initiation and elongation in C2C12 myoblasts.

    Mol. Cells   30: 513-518   2010年

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  • Myonucleus-Related Properties in Soleus Muscle Fibers of mdx Mice

    Masahiro Terada, Yong Bo Lan, Fuminori Kawano, Takashi Ohira, Yoko Higo, Naoya Nakai, Kazuhiko Imaizumi, Akihiko Ogura, Norihiro Nishimoto, Yasuo Adachi, Yoshinobu Ohira

    CELLS TISSUES ORGANS   191 ( 3 )   248 - 259   2010年

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    記述言語:英語   出版者・発行元:KARGER  

    Distribution and total number of myonuclei in single soleus muscle fibers, sampled from tendon to tendon, were analyzed in mdx and wild-type (WT) mice. Apoptotic myonuclei and the microscopic structure around the myonuclei were also analyzed. Three types of muscle fibers of mdx mice with myonuclear distribution at either central, peripheral, or both central and peripheral regions were observed in the longitudinal analyses. All of the myonuclei were located at the peripheral region in WT mice. The total number of myonuclei counted in the whole length of fibers with peripheral myonuclei only was 17% less in mdx than in WT mice (p &lt; 0.05). But the total myonuclear numbers in mdx mouse fibers with different distribution (peripheral vs. central) of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Myonuclei located between the center and peripheral regions were also seen in the cross-sectional analyses of muscle fibers. The cross-sectional area and length of fibers, sarcomere number, myonuclear size, myosin heavy chain expression, satellite cell number and neuromuscular junction were identical between each type of fiber. Apoptosis was not detected in any myonuclei located either in central or peripheral regions of muscle fibers. Thus, it was suggested that apoptosis-related loss of central myonuclei and regeneration-related new accretion at the peripheral region is not the cause of different distribution of myonuclei seen in muscle fibers in mdx mice. However, it was speculated that cross-sectional migration of myonuclei from central to peripheral regions may be induced in response to regeneration, because the total myonuclear numbers in fibers with different distribution of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Further, myonuclei located between the center and peripheral regions were also seen. However, the question remains as to how or why nuclei might migrate to the periphery in a regenerating muscle fiber, since there was no microscopic evidence of any structural changes around the myonuclei that may be responsible for the movement of the nucleus. Copyright (C) 2009 S. Karger AG, Basel

    DOI: 10.1159/000240245

    Web of Science

  • Myonucleus-Related Properties in Soleus Muscle Fibers of mdx Mice

    Masahiro Terada, Yong Bo Lan, Fuminori Kawano, Takashi Ohira, Yoko Higo, Naoya Nakai, Kazuhiko Imaizumi, Akihiko Ogura, Norihiro Nishimoto, Yasuo Adachi, Yoshinobu Ohira

    CELLS TISSUES ORGANS   191 ( 3 )   248 - 259   2010年

     詳細を見る

    記述言語:英語   出版者・発行元:KARGER  

    Distribution and total number of myonuclei in single soleus muscle fibers, sampled from tendon to tendon, were analyzed in mdx and wild-type (WT) mice. Apoptotic myonuclei and the microscopic structure around the myonuclei were also analyzed. Three types of muscle fibers of mdx mice with myonuclear distribution at either central, peripheral, or both central and peripheral regions were observed in the longitudinal analyses. All of the myonuclei were located at the peripheral region in WT mice. The total number of myonuclei counted in the whole length of fibers with peripheral myonuclei only was 17% less in mdx than in WT mice (p &lt; 0.05). But the total myonuclear numbers in mdx mouse fibers with different distribution (peripheral vs. central) of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Myonuclei located between the center and peripheral regions were also seen in the cross-sectional analyses of muscle fibers. The cross-sectional area and length of fibers, sarcomere number, myonuclear size, myosin heavy chain expression, satellite cell number and neuromuscular junction were identical between each type of fiber. Apoptosis was not detected in any myonuclei located either in central or peripheral regions of muscle fibers. Thus, it was suggested that apoptosis-related loss of central myonuclei and regeneration-related new accretion at the peripheral region is not the cause of different distribution of myonuclei seen in muscle fibers in mdx mice. However, it was speculated that cross-sectional migration of myonuclei from central to peripheral regions may be induced in response to regeneration, because the total myonuclear numbers in fibers with different distribution of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Further, myonuclei located between the center and peripheral regions were also seen. However, the question remains as to how or why nuclei might migrate to the periphery in a regenerating muscle fiber, since there was no microscopic evidence of any structural changes around the myonuclei that may be responsible for the movement of the nucleus. Copyright (C) 2009 S. Karger AG, Basel

    DOI: 10.1159/000240245

    Web of Science

  • Effects of macrophage on unloading/reloading-related regulation of muscle fiber size in op/op mice

    Takashi Ohira, Xiao Dong Wang, Fuminori Kawano, Masahiro Terada, Hiroshi Yamamoto, Tsunekata Ito, Naoya Nakai, Katsumasa Goto, Yoshinobu Ohira

    FASEB JOURNAL   23   2009年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Neural and/or mechanical responses of adductor longus muscle to exposure to microgravity in Wistar Hannover rats

    Jpn. J. Aerospace Environ. Med.   46: 21-28, 2009.   2009年

  • Neural and/or mechanical responses of adductor longus muscle to exposure to microgravity in Wistar Hannover rats

    Jpn. J. Aerospace Environ. Med.   46: 21-28, 2009.   2009年

  • Effects of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists on leucine-induced phosphorylation of translational targets in C2C12 cells

    Naoya Nakai, Fuminori Kawano, Masahiro Terada, Yoshihiko Oke, Takashi Ohira, Yoshinobu Ohira

    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS   1780 ( 10 )   1101 - 1105   2008年10月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Effect of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, WY-14,643 (WY) and/or clofibrate, on the leucine-induced phosphorylation of translational targets in C2C12 myoblasts was studied. C2C12 cells were treated with WY or clofibrate for 24 h prior to stimulation with leucine. Western blot analyses revealed that the leucine-induced phosphorylation of p70 S6 kinase (p70S6K), a key regulator of translation initiation, was significantly higher in WY-treated cells than in control and clofibrate-treated cells. Phosphorylation of extracellular-regulated kinase (ERK1/2) was higher in WY-treated cells. WY treatment also increased the leucine-induced phosphorylation of ribosomal protein S6 and eukaryotic initiation factor 4B. In contrast, eukaryotic elongation factor 2, a marker for peptide chain elongation process, was significantly activated (dephosphorylated) only in leucine-stimulated control cells. Pre-treatment of the cells with PD98059 (ERK1/2 kinase inhibitor) prevented the phosphorylation of ERK1/2 and decreased the leucine-induced phosphorylation of p70S6K. It is concluded that WY increased the leucine-induced phosphorylation of target proteins involving in translation initiation via ERK/p70S6K pathway, but impaired the signaling for elongation process, suggesting that p70S6K phosphorylation may be essential, but not sufficient for the activation of entire targets for protein translation in WY-treated cells. (C) 2008 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.bbagen.2008.06.002

    Web of Science

  • Essential role of satellite cells in the growth of rat soleus muscle fibers

    Fuminori Kawano, Yoshiaki Takeno, Naoya Nakai, Yoko Higo, Masahiro Terada, Takashi Ohira, Ikuya Nonaka, Yoshinobu Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C458 - C467   2008年8月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of gravitational loading or unloading on the growth-associated increase in the cross-sectional area and length of fibers, as well as the total fiber number, in soleus muscle were studied in rats. Furthermore, the roles of satellite cells and myonuclei in growth of these properties were also investigated. The hindlimb unloading by tail suspension was performed in newborn rats from postnatal day 4 to month 3 with or without 3-mo reloading. The morphological properties were measured in whole muscle and/or single fibers sampled from tendon to tendon. Growth-associated increases of soleus weight and fiber cross-sectional area in the unloaded group were similar to 68% and 69% less than the age-matched controls. However, the increases of number and length of fibers were not influenced by unloading. Growth-related increases of the number of quiescent satellite cells and myonuclei were inhibited by unloading. And the growth-related decrease of mitotically active satellite cells, seen even in controls (20%, P &gt; 0.05), was also stimulated (80%). The increase of myonuclei during 3-mo unloading was only 40 times vs. 92 times in controls. Inhibited increase of myonuclear number was not related to apoptosis. The size of myonuclear domain in the unloaded group was less and that of single nuclei, which was decreased by growth, was larger than controls. However, all of these parameters, inhibited by unloading, were increased toward the control levels generally by reloading. It is suggested that the satellite cell-related stimulation in response to gravitational loading plays an essential role in the cross-sectional growth of soleus muscle fibers.

    DOI: 10.1152/ajpcell.00497.2007

    Web of Science

  • Essential role of satellite cells in the growth of rat soleus muscle fibers

    Fuminori Kawano, Yoshiaki Takeno, Naoya Nakai, Yoko Higo, Masahiro Terada, Takashi Ohira, Ikuya Nonaka, Yoshinobu Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C458 - C467   2008年8月

     詳細を見る

    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of gravitational loading or unloading on the growth-associated increase in the cross-sectional area and length of fibers, as well as the total fiber number, in soleus muscle were studied in rats. Furthermore, the roles of satellite cells and myonuclei in growth of these properties were also investigated. The hindlimb unloading by tail suspension was performed in newborn rats from postnatal day 4 to month 3 with or without 3-mo reloading. The morphological properties were measured in whole muscle and/or single fibers sampled from tendon to tendon. Growth-associated increases of soleus weight and fiber cross-sectional area in the unloaded group were similar to 68% and 69% less than the age-matched controls. However, the increases of number and length of fibers were not influenced by unloading. Growth-related increases of the number of quiescent satellite cells and myonuclei were inhibited by unloading. And the growth-related decrease of mitotically active satellite cells, seen even in controls (20%, P &gt; 0.05), was also stimulated (80%). The increase of myonuclei during 3-mo unloading was only 40 times vs. 92 times in controls. Inhibited increase of myonuclear number was not related to apoptosis. The size of myonuclear domain in the unloaded group was less and that of single nuclei, which was decreased by growth, was larger than controls. However, all of these parameters, inhibited by unloading, were increased toward the control levels generally by reloading. It is suggested that the satellite cell-related stimulation in response to gravitational loading plays an essential role in the cross-sectional growth of soleus muscle fibers.

    DOI: 10.1152/ajpcell.00497.2007

    Web of Science

  • Essential role of satellite cells in the growth of rat soleus muscle fibers

    Fuminori Kawano, Yoshiaki Takeno, Naoya Nakai, Yoko Higo, Masahiro Terada, Takashi Ohira, Ikuya Nonaka, Yoshinobu Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C458 - C467   2008年8月

     詳細を見る

    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of gravitational loading or unloading on the growth-associated increase in the cross-sectional area and length of fibers, as well as the total fiber number, in soleus muscle were studied in rats. Furthermore, the roles of satellite cells and myonuclei in growth of these properties were also investigated. The hindlimb unloading by tail suspension was performed in newborn rats from postnatal day 4 to month 3 with or without 3-mo reloading. The morphological properties were measured in whole muscle and/or single fibers sampled from tendon to tendon. Growth-associated increases of soleus weight and fiber cross-sectional area in the unloaded group were similar to 68% and 69% less than the age-matched controls. However, the increases of number and length of fibers were not influenced by unloading. Growth-related increases of the number of quiescent satellite cells and myonuclei were inhibited by unloading. And the growth-related decrease of mitotically active satellite cells, seen even in controls (20%, P &gt; 0.05), was also stimulated (80%). The increase of myonuclei during 3-mo unloading was only 40 times vs. 92 times in controls. Inhibited increase of myonuclear number was not related to apoptosis. The size of myonuclear domain in the unloaded group was less and that of single nuclei, which was decreased by growth, was larger than controls. However, all of these parameters, inhibited by unloading, were increased toward the control levels generally by reloading. It is suggested that the satellite cell-related stimulation in response to gravitational loading plays an essential role in the cross-sectional growth of soleus muscle fibers.

    DOI: 10.1152/ajpcell.00497.2007

    Web of Science

  • Essential role of satellite cells in the growth of rat soleus muscle fibers

    Fuminori Kawano, Yoshiaki Takeno, Naoya Nakai, Yoko Higo, Masahiro Terada, Takashi Ohira, Ikuya Nonaka, Yoshinobu Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   295 ( 2 )   C458 - C467   2008年8月

     詳細を見る

    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of gravitational loading or unloading on the growth-associated increase in the cross-sectional area and length of fibers, as well as the total fiber number, in soleus muscle were studied in rats. Furthermore, the roles of satellite cells and myonuclei in growth of these properties were also investigated. The hindlimb unloading by tail suspension was performed in newborn rats from postnatal day 4 to month 3 with or without 3-mo reloading. The morphological properties were measured in whole muscle and/or single fibers sampled from tendon to tendon. Growth-associated increases of soleus weight and fiber cross-sectional area in the unloaded group were similar to 68% and 69% less than the age-matched controls. However, the increases of number and length of fibers were not influenced by unloading. Growth-related increases of the number of quiescent satellite cells and myonuclei were inhibited by unloading. And the growth-related decrease of mitotically active satellite cells, seen even in controls (20%, P &gt; 0.05), was also stimulated (80%). The increase of myonuclei during 3-mo unloading was only 40 times vs. 92 times in controls. Inhibited increase of myonuclear number was not related to apoptosis. The size of myonuclear domain in the unloaded group was less and that of single nuclei, which was decreased by growth, was larger than controls. However, all of these parameters, inhibited by unloading, were increased toward the control levels generally by reloading. It is suggested that the satellite cell-related stimulation in response to gravitational loading plays an essential role in the cross-sectional growth of soleus muscle fibers.

    DOI: 10.1152/ajpcell.00497.2007

    Web of Science

  • Effects of mechanical overloading on the properties of soleus muscle fibers, with or without damage, in mdx and wild type mice

    M.. Terada, F. Kawano, T. Ohira, Y. Oke, N. Nakai, Y. Ohira

    J. Gravit. Physiol. Proc. of 10th ESA the ‘Life in Space for Life on Earth Symposium’   15   97 - 98   2008年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

  • Effects of peroxisome proliferator-activated receptor α (PPAR α) agonists on leucine-induced phosphorylation of translational targets in C2C12 cells.

    2008年

  • Effects of peroxisome proliferator-activated receptor α (PPAR α) agonists on leucine-induced phosphorylation of translational targets in C2C12 cells.

    2008年

  • Effects of peroxisome proliferator-activated receptor alpha (PPARalpha) agonists on leucine-induced phosphorylation of translational targets in C2C12 cells

    Biochim. Biophys. Acta,   1780: 1101-1105   2008年

  • 210. ペルオキシソーム増殖因子活性化受容体α(PPARα)作動薬であるWY-14,643はロイシンによるタンパク質合成促進シグナルを増強する(代謝,第62回日本体力医学会大会)

    中井 直也, 大平 充宣

    体力科學   56 ( 6 )   683 - 683   2007年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • The characters of soleus muscle fibers of mdx mice with different distribution of myonuclei

    M. Terada, F. Kawano, Y. Higo, T. Ohira, X. Wang, N. Nakai, Y. Ohira

    NEUROMUSCULAR DISORDERS   17 ( 9-10 )   805 - 806   2007年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    DOI: 10.1016/j.nmd.2007.06.151

    Web of Science

  • Peroxisome proliferators-activated receptor alpha (PPAR alpha) agonist, WY-14,643, increased leucine-induced activation of translation initiation in C2C12 cells

    N. Nakai, F. Kawano, M. Terada, Y. Ohira

    NEUROMUSCULAR DISORDERS   17 ( 9-10 )   897 - 897   2007年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    DOI: 10.1016/j.nmd.2007.06.451

    Web of Science

  • Clinical aspects of physical exercise for diabetes/metabolic syndrome

    Yuzo Sato, Masaru Nagasaki, Masakazu Kubota, Tomoko Uno, Naoya Nakai

    DIABETES RESEARCH AND CLINICAL PRACTICE   77   S87 - S91   2007年9月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In the field of diabetes and exercise, among the epidemiological studies of physical exercise, recent mega-trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant correlation has been observed between delta MCR (Delta insulin sensitivity) and the average number of steps performed in a day. Our recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in part, to increases in GLUT4 protein, IRS1 and P13-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise of mild to moderate intensity, including walking and jogging, 10-30 min a day, 3-5 days a week, is recommended. Resistance training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related diseases. (c) 2007 Published by Elsevier Ireland Ltd.

    DOI: 10.1016/j.diabres.2007.01.039

    Web of Science

  • Clinical aspects of physical exercise for diabetes/metabolic syndrome

    Yuzo Sato, Masaru Nagasaki, Masakazu Kubota, Tomoko Uno, Naoya Nakai

    DIABETES RESEARCH AND CLINICAL PRACTICE   77   S87 - S91   2007年9月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Evidence-based medicine (EBM) has come to be regarded as essential in all fields of medical sciences and practical medicine. In the field of diabetes and exercise, among the epidemiological studies of physical exercise, recent mega-trials such as the Diabetes Prevention Program (DPP) in the U.S. have shown that lifestyle intervention programs involving diet and/or exercise reduce the progression of impaired glucose tolerance (IGT) to type 2 diabetes. In studies examining the endocrinological and metabolic effects of exercise, it has been demonstrated that physical exercise promotes the utilization of blood glucose and free fatty acids in muscles and lowers blood glucose levels in well-controlled diabetic patients. Long-term, mild, regular jogging increases the action of insulin in both carbohydrate and lipid metabolism without influencing body mass index or maximal oxygen uptake. A significant correlation has been observed between delta MCR (Delta insulin sensitivity) and the average number of steps performed in a day. Our recent data suggested that the improved effectiveness of insulin that occurs as a result of physical exercise is attributable, at least in part, to increases in GLUT4 protein, IRS1 and P13-kinase protein in skeletal muscle. As a prescription for exercise, aerobic exercise of mild to moderate intensity, including walking and jogging, 10-30 min a day, 3-5 days a week, is recommended. Resistance training of mild intensity with the use of light dumbbells and stretch cords should be combined in elderly individuals who have decreased muscle strength. An active lifestyle is essential in the management of diabetes, which is one of typical lifestyle-related diseases. (c) 2007 Published by Elsevier Ireland Ltd.

    DOI: 10.1016/j.diabres.2007.01.039

    Web of Science

  • Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass

    F. Kawano, Y. Matsuoka, Y. Oke, Y. Higo, M. Terada, X. D. Wang, N. Nakai, H. Fukuda, S. Imajoh-Ohmi, Y. Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 1 )   C35 - C44   2007年7月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1 - 2 to 3 - 5) within a myonucleus and myonuclear domain (+ 27%) compared with the preexperimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+ 84%) and HSP27 (+ 28%). Fiber atrophy (+ 52%), associated with decreased number (+ 31%) and domain size (+ 28%) of myonuclei and phosphorylation of S6 (- 98%) and HSP27 (- 63%), and with increased myonuclear size (+ 19%) and ubiquitination of myosin heavy chain (+ 33%, P &gt; 0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (- 47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+ 18%) by addition of synergist ablation, even though the integrated electromyogram level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.

    DOI: 10.1152/ajpcell.00297.2006

    Web of Science

  • Role(s) of nucleoli and phosphorylation of ribosomal protein S6 and/or HSP27 in the regulation of muscle mass

    F. Kawano, Y. Matsuoka, Y. Oke, Y. Higo, M. Terada, X. D. Wang, N. Nakai, H. Fukuda, S. Imajoh-Ohmi, Y. Ohira

    AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY   293 ( 1 )   C35 - C44   2007年7月

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    記述言語:英語   出版者・発行元:AMER PHYSIOLOGICAL SOC  

    Effects of 14 days of hindlimb unloading or synergist ablation-related overloading with or without deafferentation on the fiber cross-sectional area, myonuclear number, size, and domain, the number of nucleoli in a single myonucleus, and the levels in the phosphorylation of the ribosomal protein S6 (S6) and 27-kDa heat shock protein (HSP27) were studied in rat soleus. Hypertrophy of fibers (+24%), associated with increased nucleolar number (from 1 - 2 to 3 - 5) within a myonucleus and myonuclear domain (+ 27%) compared with the preexperimental level, was induced by synergist ablation. Such phenomena were associated with increased levels of phosphorylated S6 (+ 84%) and HSP27 (+ 28%). Fiber atrophy (+ 52%), associated with decreased number (+ 31%) and domain size (+ 28%) of myonuclei and phosphorylation of S6 (- 98%) and HSP27 (- 63%), and with increased myonuclear size (+ 19%) and ubiquitination of myosin heavy chain (+ 33%, P &gt; 0.05), was observed after unloading, which inhibited the mechanical load. Responses to deafferentation, which inhibited electromyogram level (- 47%), were basically similar to those caused by hindlimb unloading, although the magnitudes were minor. The deafferentation-related responses were prevented and nucleolar number was even increased (+ 18%) by addition of synergist ablation, even though the integrated electromyogram level was still 30% less than controls. It is suggested that the load-dependent maintenance or upregulation of the nucleolar number and/or phosphorylation of S6 and HSP27 plays the important role(s) in the regulation of muscle mass. It was also indicated that such regulation was not necessarily associated with the neural activity.

    DOI: 10.1152/ajpcell.00297.2006

    Web of Science

  • Leucine-induced activation of translational initiation is partly regulated by the branched-chain alpha-keto acid dehydrogenase complex in C2C12 cells

    N Nakai, Y Shimomura, T Tamura, N Tamura, K Hamada, F Kawano, Y Ohlra

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   343 ( 4 )   1244 - 1250   2006年5月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. The complex contains El (alpha 2 beta 2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1 alpha subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2Cl2 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results Suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2006.03.074

    Web of Science

  • Leucine-induced activation of translational initiation is partly regulated by the branched-chain alpha-keto acid dehydrogenase complex in C2C12 cells

    N Nakai, Y Shimomura, T Tamura, N Tamura, K Hamada, F Kawano, Y Ohlra

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   343 ( 4 )   1244 - 1250   2006年5月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. The complex contains El (alpha 2 beta 2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1 alpha subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2Cl2 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48 h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results Suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex. (c) 2006 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.bbrc.2006.03.074

    Web of Science

  • Activation of the p70 S6 kinase by leucine is partly regulated by the activity of branched-chain a-keto acid dehydrogenase (BCKDH) complex

    N Nakai, Y Shimomura, T Tamura, N Tamura, K Hamada, F Kawano, Y Ohira

    FASEB JOURNAL   20 ( 4 )   A161 - A161   2006年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Mechanical stress-dependent transformation of nucleoli in myonuclei of rat soleus muscle fibers

    F. Kawano, Y. Matsuoka, Y. Oke, Y. Higo, M. Terada, X. D. Wang, Y. B. Lan, N. Nakai, Y. Ohira

    J. Gravit. Physiol. Proc. of 27th Annual International Gravitational Physiology Meeting   13 ( 1 )   85 - 86   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)  

  • 221.ロイシンによるタンパク合成促進作用におけるbranched-chain α-keto acid dehydrogenase (BCKDH)の役割(栄養・消化,一般口演,第60回 日本体力医学会大会)

    中井 直也, 下村 吉治, 村上 太郎, 濱田 広一郎, 吉田 敬義, 大平 充宣

    体力科學   54 ( 6 )   529 - 529   2005年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver

    M Tanaka, M Suzuki, T Kawana, M Segawa, M Yoshikawa, M Mori, M Kobayashi, N Nakai, TR Saito

    JOURNAL OF MOLECULAR ENDOCRINOLOGY   34 ( 3 )   667 - 673   2005年6月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    In addition to the known four alternative first exons E1(1), E1(2), E1(3) and E1(4) of the rat prolactin receptor (PRL-R) gene, a novel first exon, E1(5), was identified by cDNA cloning of the 5'-end region of PRL-R mRNA in the rat liver. Genomic fragments containing E1(5) and its 5'- or 3'-flanking regions were also cloned from rat kidney genomic DNA. A sequence search for E1(5) revealed that E1(5) is located 49 kb upstream of exon 2 of the PRL-R gene in rat chromosome 2q16. RT-PCR analysis revealed that El. was preferentially expressed in the liver, brain and kidney. Expression profiles of E1(2)-, E1(3)- and E1(5)-PRL-R mRNAs in the liver of male and female rats at 5 days of age and those at 8 weeks of age were examined by RT-PCR. The levels of E1(2)-PRL-R mRNA in the female rat increased remarkably in rats at 8 weeks of age compared with those at 5 days of age, and the levels of E1(2)-PRL-R mRNA in the male rat decreased markedly at 8 weeks of age compared with those at 5 days of age. In the female rat, the levels of El 2-PRL-R mRNA at 8 weeks of age decreased with ovariectomy performed at 4 weeks of age and recovered with the administration of P-oestradiol. On the contrary, the levels of E1(5)-PRL-R mRNA increased with ovariectomy and decreased with the oestrogen treatment. In the male rat liver, the levels of E1(2)-PRL-R mRNA at 8 weeks of age increased strikingly with castration performed at 4 weeks of age and became undetectable with the administration of testosterone. The levels of E1(5)-PRL-R mRNA increased slightly with castration and were restored by testosterone treatment. Removal of gonadal tissues and sex steroid hormone treatment had no effect on the expression levels of E1(3)-PRL-R mRNA in both female and male rat livers. These results indicated that the expression of the PRL-R gene in the liver is regulated by the differential effects of sex steroid hormones on the transcription of the multiple first exons including the novel one.

    DOI: 10.1677/jme.1.01702

    Web of Science

  • Differential effects of sex steroid hormones on the expression of multiple first exons including a novel first exon of prolactin receptor gene in the rat liver

    M Tanaka, M Suzuki, T Kawana, M Segawa, M Yoshikawa, M Mori, M Kobayashi, N Nakai, TR Saito

    JOURNAL OF MOLECULAR ENDOCRINOLOGY   34 ( 3 )   667 - 673   2005年6月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    In addition to the known four alternative first exons E1(1), E1(2), E1(3) and E1(4) of the rat prolactin receptor (PRL-R) gene, a novel first exon, E1(5), was identified by cDNA cloning of the 5'-end region of PRL-R mRNA in the rat liver. Genomic fragments containing E1(5) and its 5'- or 3'-flanking regions were also cloned from rat kidney genomic DNA. A sequence search for E1(5) revealed that E1(5) is located 49 kb upstream of exon 2 of the PRL-R gene in rat chromosome 2q16. RT-PCR analysis revealed that El. was preferentially expressed in the liver, brain and kidney. Expression profiles of E1(2)-, E1(3)- and E1(5)-PRL-R mRNAs in the liver of male and female rats at 5 days of age and those at 8 weeks of age were examined by RT-PCR. The levels of E1(2)-PRL-R mRNA in the female rat increased remarkably in rats at 8 weeks of age compared with those at 5 days of age, and the levels of E1(2)-PRL-R mRNA in the male rat decreased markedly at 8 weeks of age compared with those at 5 days of age. In the female rat, the levels of El 2-PRL-R mRNA at 8 weeks of age decreased with ovariectomy performed at 4 weeks of age and recovered with the administration of P-oestradiol. On the contrary, the levels of E1(5)-PRL-R mRNA increased with ovariectomy and decreased with the oestrogen treatment. In the male rat liver, the levels of E1(2)-PRL-R mRNA at 8 weeks of age increased strikingly with castration performed at 4 weeks of age and became undetectable with the administration of testosterone. The levels of E1(5)-PRL-R mRNA increased slightly with castration and were restored by testosterone treatment. Removal of gonadal tissues and sex steroid hormone treatment had no effect on the expression levels of E1(3)-PRL-R mRNA in both female and male rat livers. These results indicated that the expression of the PRL-R gene in the liver is regulated by the differential effects of sex steroid hormones on the transcription of the multiple first exons including the novel one.

    DOI: 10.1677/jme.1.01702

    Web of Science

  • Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson's disease in rats

    T Fujikawa, S Miguchi, N Kanada, N Nakai, M Ogata, Suzuki, I, K Nakashima

    JOURNAL OF ETHNOPHARMACOLOGY   97 ( 2 )   375 - 381   2005年2月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The aim of this study was to determine whether Acanthopanax senticosus Harms (ASH) offers protection against Parkinson's disease (PD) and its related depressive behaviors in rats administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We examined how ASH affected the MPTP-induced loss of tyrosine hydroxylase (TH)-positive neurons in the midbrain of rats. Extract from the stem bark of ASH prepared with hot water was dissolved in distilled water. Rats were then orally administered ASH (250 mg/kg) once a day for 2 weeks before ASH administration Plus an intraperitoneal injection of MPTP (20 mg/ka). The pole test and catalepsy test were used to evaluate the effects of ASH administration on bradykinesia and depressive behaviors in the PD model of rats given MPTP for 2 weeks. Treatment with ASH for 2 weeks resulted in prophylactic effects on MPTP-induced Parkinsonian bradykinesia and catalepsy. Immunohistochemistical analysis using TH antibody showed that ASH provided cytoprotective effects against MPTP-induced loss of dopamine (DA) cells. The present results suggest that it may be possible to use ASH for the prevention of nigral degenerative disorders, e.g., PD with depression, caused by exposure to toxic substances. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.jep.2004.11.031

    Web of Science

  • Acanthopanax senticosus Harms as a prophylactic for MPTP-induced Parkinson’s disease in rats.

    J. Ethnopharmacol.   97 ( 2 )   375 - 381   2005年2月

     詳細を見る

    記述言語:英語  

    DOI: 10.1016/j.jep.2004.11.031

    Web of Science

  • Estrogen controls branched-chain amino acid catabolism in female rats

    M Obayashi, Y Shimomura, N Nakai, NH Jeoung, M Nagasaki, T Murakami, Y Sato, RA Harris

    JOURNAL OF NUTRITION   134 ( 10 )   2628 - 2633   2004年10月

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    記述言語:英語   出版者・発行元:AMER INST NUTRITION  

    A diurnal rhythm occurs in the activity state of branched-chain a-keto acid dehydrogenase complex (BCKDC) in female but not male rats. We attempted to determine the role played by ovarian hormones in this difference in enzyme regulation. A series of experiments examined the effects of the 4-d estrous cycle, ovariectomy, and replacement of female sex steroids on the catabolism of BCAAS. A proestrous decrease in the activity state of the complex corresponded to an increase in the plasma 17beta-estradiol level. Withdrawal of gonadal steroids by ovariectomy resulted in an increase in the activity state of BCKDC and a decrease in the activity of the branched-chain a-keto acid dehydrogenase kinase (BDK). However, 17beta-estradiol reversed these effects, resulting in an increase in the BDK activity, thereby decreasing the activity of the complex. Progesterone administration was ineffective. The changes in the percentage of active BCKDC caused by 17beta-estradiol withdrawal and replacement resulted from changes in the amount of BDK protein associated with the complex and therefore its activity. Thus, the marked diurnal variation in the activity state of BCKDC exhibited by female rats involves estrogenic control of BDK activity. We hypothesize that the 17beta-estradiol-controlled feeding pattern produces these variations in BCKDC activity. This may function in female rats to conserve essential amino acids for protein synthesis.

    DOI: 10.1093/jn/134.10.2628

    Web of Science

  • Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line

    N Nakai, M Kaneko, N Nakao, T Fujikawa, K Nakashima, M Ogata, M Tanaka

    LIFE SCIENCES   75 ( 18 )   2193 - 2201   2004年9月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Ghrelin, an endogenous ligand for growth hormone (GH) secretagogue receptor, stimulates GH secretion. The ghrelin gene is expressed most abundantly in stomach. The mRNA is also detected in other tissues and cell lines. However, the mechanism of the transcriptional regulation of the ghrelin gene has not yet been clarified. In the present study, we have investigated the regulatory region of the ghrelin gene expression in the human medullary thyroid carcinoma cell line (TT cells). PCR analysis of the 5'-region for human ghrelin gene revealed the presence of the first exon corresponding to the short non-coding first exon of the mouse ghrelin gene. The first exon is located at the 502 by upstream from the 5'-end of the formerly reported human ghrelin gene. RT PCR analysis showed the expression of the first exon in the stomach and TT cells. The expression of the first exon in the human stomach was confirmed by 5'-RACE method. Significant level of promoter activity was observed in the 1225-1107 by up-stream region of the translation initiation site by luciferase assay. Specific protein binding to the promoter region of -1129 to -1100 was detected by electrophoretic mobility shift assay with nuclear extract from TT cells. These results suggest that the ghrelin gene expression in TT cells might be regulated by the upstream region of the first exon. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.lfs.2004.04.028

    Web of Science

  • Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line

    N Nakai, M Kaneko, N Nakao, T Fujikawa, K Nakashima, M Ogata, M Tanaka

    LIFE SCIENCES   75 ( 18 )   2193 - 2201   2004年9月

     詳細を見る

    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Ghrelin, an endogenous ligand for growth hormone (GH) secretagogue receptor, stimulates GH secretion. The ghrelin gene is expressed most abundantly in stomach. The mRNA is also detected in other tissues and cell lines. However, the mechanism of the transcriptional regulation of the ghrelin gene has not yet been clarified. In the present study, we have investigated the regulatory region of the ghrelin gene expression in the human medullary thyroid carcinoma cell line (TT cells). PCR analysis of the 5'-region for human ghrelin gene revealed the presence of the first exon corresponding to the short non-coding first exon of the mouse ghrelin gene. The first exon is located at the 502 by upstream from the 5'-end of the formerly reported human ghrelin gene. RT PCR analysis showed the expression of the first exon in the stomach and TT cells. The expression of the first exon in the human stomach was confirmed by 5'-RACE method. Significant level of promoter activity was observed in the 1225-1107 by up-stream region of the translation initiation site by luciferase assay. Specific protein binding to the promoter region of -1129 to -1100 was detected by electrophoretic mobility shift assay with nuclear extract from TT cells. These results suggest that the ghrelin gene expression in TT cells might be regulated by the upstream region of the first exon. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.lfs.2004.04.028

    Web of Science

  • Identification of promoter region of ghrelin gene in human medullary thyroid carcinoma cell line

    N Nakai, M Kaneko, N Nakao, T Fujikawa, K Nakashima, M Ogata, M Tanaka

    LIFE SCIENCES   75 ( 18 )   2193 - 2201   2004年9月

     詳細を見る

    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Ghrelin, an endogenous ligand for growth hormone (GH) secretagogue receptor, stimulates GH secretion. The ghrelin gene is expressed most abundantly in stomach. The mRNA is also detected in other tissues and cell lines. However, the mechanism of the transcriptional regulation of the ghrelin gene has not yet been clarified. In the present study, we have investigated the regulatory region of the ghrelin gene expression in the human medullary thyroid carcinoma cell line (TT cells). PCR analysis of the 5'-region for human ghrelin gene revealed the presence of the first exon corresponding to the short non-coding first exon of the mouse ghrelin gene. The first exon is located at the 502 by upstream from the 5'-end of the formerly reported human ghrelin gene. RT PCR analysis showed the expression of the first exon in the stomach and TT cells. The expression of the first exon in the human stomach was confirmed by 5'-RACE method. Significant level of promoter activity was observed in the 1225-1107 by up-stream region of the translation initiation site by luciferase assay. Specific protein binding to the promoter region of -1129 to -1100 was detected by electrophoretic mobility shift assay with nuclear extract from TT cells. These results suggest that the ghrelin gene expression in TT cells might be regulated by the upstream region of the first exon. (C) 2004 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.lfs.2004.04.028

    Web of Science

  • Characterization of structure and expression of the growth hormone receptor gene of the Japanese flounder (Paralichtys olivaceus)

    N Nakao, Y Higashimoto, T Ohkubo, H Yoshizato, N Nakai, K Nakashima, M Tanaka

    JOURNAL OF ENDOCRINOLOGY   182 ( 1 )   157 - 164   2004年7月

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    記述言語:英語   出版者・発行元:SOC ENDOCRINOLOGY  

    Growth hormone receptor (GHR) cDNA and gene of the Japanese flounder (Paralicthys olivaceus) were cloned and their molecular structures were characterized. The 641 amino acid sequence predicted from the cDNA sequence showed more than 75% overall sequence similarity with GHRs of other teleosts such as turbot and goldfish, and contained common structural features of vertebrate GHRs. The extracellular domain of flounder GHR had three pairs of cysteines and an FGEFS motif with a replacement E to D. The cytoplasmic domain contained two conserved motifs referred to as box 1 and box 2. The flounder GHR gene was cloned by PCR using primers designed from the sequence of the GHR cDNA. The GHR gene was composed of 10 exons. The sequence of exon 1 corresponded to the 5'-untranslated region of the cDNA, and exons 2-6 encoded most parts of the extracellular domain. The transmembrane domain was found in exon 7, and the intracellular domain was encoded in exons 8-10. Exon 10 also encoded the 3'-untranslated region. Comparison of the flounder GHR gene with the human GHR gene shows that the flounder gene contains no exons corresponding to exon 3 of the human GHR gene, and that the region corresponding to exon 10 in the human GHR gene is encoded by exons 9 and 10 in the flounder GHR gene. These findings indicate that the flounder GHR gene diverged from those of mammalian and avian GHR genes, especially in the organization of the exons encoding the cytoplasmic domain. In addition to the regular form of GHR mRNA, a 3'-truncated form lacking the region derived from exons 9 and 10 was detected as a minor species in the liver by RT-PCR and by RNase protection assay. RT-PCR analysis showed that both the regular and the 3'-truncated GHR mRNAs are expressed in a wide range of flounder tissues with the highest levels being found in the liver. The 5'-flanking region of the flounder GHR gene was cloned by inverse PCR, and three transcription start points were identified with similar frequency by RNase protection assay.

    DOI: 10.1677/joe.0.1820157

    Web of Science

  • Exercise promotes BCAA catabolism: Effects of BCAA supplementation on skeletal muscle during exercise

    Y Shimomura, T Murakami, N Nakai, M Nagasaki, RA Harris

    JOURNAL OF NUTRITION   134 ( 6 )   1583S - 1587S   2004年6月

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    記述言語:英語   出版者・発行元:AMER INST NUTRITION  

    Branched-chain amino acids (BCAAs) are essential amino acids that can be oxidized in skeletal muscle. It is known that BCAA oxidation is promoted by exercise. The mechanism responsible for this phenomenon is attributed to activation of the branched-chain a-keto acid dehydrogenase (BCKDH) complex, which catalyzes the second-step reaction of the BCAA catabolic pathway and is the rate-limiting enzyme in the pathway. This enzyme complex is regulated by a phosphorylation-dephosphorylation cycle. The BCKDH kinase is responsible for inactivation of the complex by phosphorylation, and the activity of the kinase is inversely correlated with the activity state of the BCKDH complex, which suggests that the kinase is the primary regulator of the complex. We found recently that administration of ligands for peroxisome proliferator-activated receptor-alpha (PPARalpha) in rats caused activation of the hepatic BCKDH complex in association with a decrease in the kinase activity, which suggests that promotion of fatty acid oxidation upregulates the BCAA catabolism. Long-chain fatty acids are ligands for PPARalpha, and the fatty acid oxidation is promoted by several physiological conditions including exercise. These findings suggest that fatty acids may be one of the regulators of BCAA catabolism and that the BCAA requirement is increased by exercise. Furthermore, BCAA supplementation before and after exercise has beneficial effects for decreasing exercise-induced muscle damage and promoting muscle-protein synthesis; this suggests the possibility that BCAAs are a useful supplement in relation to exercise and sports.

    Web of Science

  • Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat

    T Fujikawa, H Soya, KLK Tamashiro, RR Sakai, BS McEwen, N Nakai, M Ogata, Suzuki, I, K Nakashima

    ENDOCRINOLOGY   145 ( 4 )   2006 - 2013   2004年4月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. Wealso show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

    DOI: 10.1210/en.2003-1446

    Web of Science

  • Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat

    T Fujikawa, H Soya, KLK Tamashiro, RR Sakai, BS McEwen, N Nakai, M Ogata, Suzuki, I, K Nakashima

    ENDOCRINOLOGY   145 ( 4 )   2006 - 2013   2004年4月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. Wealso show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

    DOI: 10.1210/en.2003-1446

    Web of Science

  • Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat

    T Fujikawa, H Soya, KLK Tamashiro, RR Sakai, BS McEwen, N Nakai, M Ogata, Suzuki, I, K Nakashima

    ENDOCRINOLOGY   145 ( 4 )   2006 - 2013   2004年4月

     詳細を見る

    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. Wealso show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

    DOI: 10.1210/en.2003-1446

    Web of Science

  • Growth hormone (GH)-stimulated insulin-like growth factor I gene expression is mediated by a tyrosine phosphorylation pathway depending on C-terminal region of human GH receptor in human GH receptor-expressing Ba/F3 cells

    H Yoshizato, M Tanaka, N Nakai, N Nakao, K Nakashima

    ENDOCRINOLOGY   145 ( 1 )   214 - 220   2004年1月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    The signaling pathway of GH-stimulated IGF-I gene expression is still unclear, although it has been reported that the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) 5b pathway plays an important role in liver IGF-I expression. In this study, the GH-dependent IGF-I gene expression and its intracellular signaling mechanism have been examined in mouse pro-B, Ba/F3 cells stably expressing human GH receptor (Ba/F3-hGHR). The IGF-I gene expression was stimulated by human GH(0.01-10 nM) in a dose-dependent fashion in Ba/F3-hGHR cells. The specific inhibitors for JAK2 remarkably suppressed the GH-induced IGF-I gene expression, but MAPK or phosphatidylinositol 3 kinase-specific inhibitors failed to block the GH stimulation of the IGF-I gene expression. However, genistein, a nonspecific tyrosine kinase inhibitor that does not inhibit JAK2 and STAT5 phosphorylation, significantly suppressed the GH-induced IGF-I gene expression. Additionally, a Ba/F3-hGHR mutant that contained the truncated C-terminal hGHR up to D351 showed no IGF-I gene expression in response to human GH. The D351 form normally has the GH-induced JAK/STAT5 tyrosine phosphorylation. These results suggest that the JAK-STAT5 pathway and the novel tyrosine phosphorylation pathway, dependent on signaling from the C-terminal region of hGHR, might be involved in the GH-stimulated IGF-I gene expression in Ba/F3 cells.

    DOI: 10.1210/en.2003-0811

    Web of Science

  • Growth hormone (GH)-stimulated insulin-like growth factor I gene expression is mediated by a tyrosine phosphorylation pathway depending on C-terminal region of human GH receptor in human GH receptor-expressing Ba/F3 cells

    H Yoshizato, M Tanaka, N Nakai, N Nakao, K Nakashima

    ENDOCRINOLOGY   145 ( 1 )   214 - 220   2004年1月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    The signaling pathway of GH-stimulated IGF-I gene expression is still unclear, although it has been reported that the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) 5b pathway plays an important role in liver IGF-I expression. In this study, the GH-dependent IGF-I gene expression and its intracellular signaling mechanism have been examined in mouse pro-B, Ba/F3 cells stably expressing human GH receptor (Ba/F3-hGHR). The IGF-I gene expression was stimulated by human GH(0.01-10 nM) in a dose-dependent fashion in Ba/F3-hGHR cells. The specific inhibitors for JAK2 remarkably suppressed the GH-induced IGF-I gene expression, but MAPK or phosphatidylinositol 3 kinase-specific inhibitors failed to block the GH stimulation of the IGF-I gene expression. However, genistein, a nonspecific tyrosine kinase inhibitor that does not inhibit JAK2 and STAT5 phosphorylation, significantly suppressed the GH-induced IGF-I gene expression. Additionally, a Ba/F3-hGHR mutant that contained the truncated C-terminal hGHR up to D351 showed no IGF-I gene expression in response to human GH. The D351 form normally has the GH-induced JAK/STAT5 tyrosine phosphorylation. These results suggest that the JAK-STAT5 pathway and the novel tyrosine phosphorylation pathway, dependent on signaling from the C-terminal region of hGHR, might be involved in the GH-stimulated IGF-I gene expression in Ba/F3 cells.

    DOI: 10.1210/en.2003-0811

    Web of Science

  • Characterization of structure and expression of the growth hormone receptor gene of the Japanese flounder (Paralichtys olivaceus).

    J Endocrinol.   2004年

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  • Estrogen Controls Branched-Chain Amino Acid Catabolism in Female Rats.

    J. Nutr.   2004年

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  • Estrogen Controls Branched-Chain Amino Acid Catabolism in Female Rats.

    J. Nutr.   134: 2628-2633   2004年

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  • ERK2 MAPキナーゼによるT細胞の局在化制御

    森良子, 田中剛広, 藤川隆彦, 中井直也, 小杉厚, 緒方正人

    日本免疫学会総会・学術集会記録   34   2004年

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  • Characterization of structure and expression of the growth hormone receptor gene of the Japanese flounder (Paralichtys olivaceus).

    J Endocrinol.   2004年

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  • GH-Stimulated Insulin-Like Growth Factor I Gene Expression is Mediated by a Tyrosine phosphorylation Pathway Depending on C-terminal Region of Human GH Receptor in Human GH Receptor-Expressing Ba/F3 Cells.

    Endocrinology   2004年

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  • Essential role for ERK2 mitogen-activated protein kinase in placental development

    N Hatano, Y Mori, M Oh-Hora, A Kosugi, T Fujikawa, N Nakai, H Niwa, J Miyazaki, T Hamaoka, M Ogata

    GENES TO CELLS   8 ( 11 )   847 - 856   2003年11月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background: Extracellular signal-regulated kinase 2 (ERK2) has been implicated in cell proliferation, differentiation, and survival. However, its role in vivo remains to be determined.
    Results: Here we show that the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta. In these animals, the labyrinthine layer of the placenta is very thin and few foetal blood vessels are observed. ERK2 mutants can be rescued by the transgenic expression of ERK2, demonstrating that these abnormalities are caused by ERK2-deficiency. Although ERK2-deficient fetuses are much smaller than wild-type littermates, this seems to be secondary to malfunction of the placenta. When the placental defect is rescued by tetraploid-aggregation, ERK2-deficient foetuses grow as well as littermate controls.
    Conclusion: These observations indicate that ERK2 is essential for placental development and suggest that ERK2 in the trophoblast compartment may be indispensable for the vascularization of the labyrinth.

    DOI: 10.1046/j.1365-2443.2003.00680.x

    Web of Science

  • Essential role for ERK2 mitogen-activated protein kinase in placental development

    N Hatano, Y Mori, M Oh-Hora, A Kosugi, T Fujikawa, N Nakai, H Niwa, J Miyazaki, T Hamaoka, M Ogata

    GENES TO CELLS   8 ( 11 )   847 - 856   2003年11月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background: Extracellular signal-regulated kinase 2 (ERK2) has been implicated in cell proliferation, differentiation, and survival. However, its role in vivo remains to be determined.
    Results: Here we show that the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta. In these animals, the labyrinthine layer of the placenta is very thin and few foetal blood vessels are observed. ERK2 mutants can be rescued by the transgenic expression of ERK2, demonstrating that these abnormalities are caused by ERK2-deficiency. Although ERK2-deficient fetuses are much smaller than wild-type littermates, this seems to be secondary to malfunction of the placenta. When the placental defect is rescued by tetraploid-aggregation, ERK2-deficient foetuses grow as well as littermate controls.
    Conclusion: These observations indicate that ERK2 is essential for placental development and suggest that ERK2 in the trophoblast compartment may be indispensable for the vascularization of the labyrinth.

    DOI: 10.1046/j.1365-2443.2003.00680.x

    Web of Science

  • Essential role for ERK2 mitogen-activated protein kinase in placental development

    N Hatano, Y Mori, M Oh-Hora, A Kosugi, T Fujikawa, N Nakai, H Niwa, J Miyazaki, T Hamaoka, M Ogata

    GENES TO CELLS   8 ( 11 )   847 - 856   2003年11月

     詳細を見る

    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING LTD  

    Background: Extracellular signal-regulated kinase 2 (ERK2) has been implicated in cell proliferation, differentiation, and survival. However, its role in vivo remains to be determined.
    Results: Here we show that the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta. In these animals, the labyrinthine layer of the placenta is very thin and few foetal blood vessels are observed. ERK2 mutants can be rescued by the transgenic expression of ERK2, demonstrating that these abnormalities are caused by ERK2-deficiency. Although ERK2-deficient fetuses are much smaller than wild-type littermates, this seems to be secondary to malfunction of the placenta. When the placental defect is rescued by tetraploid-aggregation, ERK2-deficient foetuses grow as well as littermate controls.
    Conclusion: These observations indicate that ERK2 is essential for placental development and suggest that ERK2 in the trophoblast compartment may be indispensable for the vascularization of the labyrinth.

    DOI: 10.1046/j.1365-2443.2003.00680.x

    Web of Science

  • Molecular characterization of chicken growth hormone secretagogue receptor gene

    M Tanaka, T Miyazaki, Yamamoto, I, N Nakai, Y Ohta, N Tsushima, M Wakita, K Shimada

    GENERAL AND COMPARATIVE ENDOCRINOLOGY   134 ( 2 )   198 - 202   2003年11月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Synthetic growth hormone secretagogues stimulate growth hormone secretion by binding to a specific receptor, growth hormone secretagogue receptor (GHS-R). In this study, we investigated the cDNA and the genomic structure of chicken GHS-R. Chicken GHS-R gene is composed of two exons separated by an intron. Two GHS-R mRNA species, cGHS-R1a and cGHS-R1a-variant (cGHS-R1aV) are generated by alternative splicing of a primary transcript. cGHS-R1a protein is predicted to have seven transmembrane domains by a high degree of amino acid sequence identity with mammalian and teleost homologs. cGHS-R1aV lacks the transmembrane-6 domain due to a 48 bp deletion. RT-PCR analysis showed widespread tissue distributions of cGHS-R1a and cGHS-R1aV mRNAs with much higher amounts of cGHS-R1a in all the tissues. (C) 2003 Elsevier Inc. All rights reserved.

    DOI: 10.1016/S0016-6480(03)00247-8

    Web of Science

  • Physical exercise improves glucose metabolism in lifestyle-related diseases

    Y Sato, M Nagasaki, N Nakai, T Fushimi

    EXPERIMENTAL BIOLOGY AND MEDICINE   228 ( 10 )   1208 - 1212   2003年11月

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    記述言語:英語   出版者・発行元:SOC EXPERIMENTAL BIOLOGY MEDICINE  

    The beneficial effects of physical exercise on the decreased insulin sensitivity caused by detrimental lifestyle were reviewed based on experimental evidences. In epidemiological studies, disease prevention has been considered at three levels: primary (avoiding the occurrence of disease), secondary (early detection and reversal), and tertiary (prevention or delay of complications). The major purpose of physical exercise for primary prevention and treatment of lifestyle-related diseases is to improve insulin sensitivity. It is known that, during physical exercise, glucose uptake by the working muscles rises 7 to 20 times over the basal level, depending on the intensity of the work performed. However, intense exercise provokes the release of insulin-counter regulatory hormones such as glucagons and catecholamines, which ultimately cause a reduction in the insulin action. Continued physical training improves the reduced peripheral tissue sensitivity to insulin in impaired glucose tolerance and Type II diabetes, along with regularization of abnormal lipid metabolism. Furthermore, combination of salt intake restriction and physical training ameliorates hypertension. In practical terms, before diabetic patients undertake any program of physical exercise, various medical examinations are needed to determine whether they have good glycemic control and are without progressive complications. Because the effect of exercise that is manifested in improved insulin sensitivity decreases within 3 days after exercise and is no longer apparent after 1 week, a continued program is needed. For a safety practice, moderate- or low-intensity exercise is preferable. In conclusion, we have found sufficient evidences that support the theory that, combined with other forms of therapy, mild exercise training increases insulin action despite no influence on body mass index or maximal oxygen uptake. Along with evident benefits in health promotion, mode rate-intensity exercise might play an important role in facilitating treatment of various diseases.

    Web of Science

  • Molecular characterization of chicken growth hormone secretagogue receptor gene

    M Tanaka, T Miyazaki, Yamamoto, I, N Nakai, Y Ohta, N Tsushima, M Wakita, K Shimada

    GENERAL AND COMPARATIVE ENDOCRINOLOGY   134 ( 2 )   198 - 202   2003年11月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Synthetic growth hormone secretagogues stimulate growth hormone secretion by binding to a specific receptor, growth hormone secretagogue receptor (GHS-R). In this study, we investigated the cDNA and the genomic structure of chicken GHS-R. Chicken GHS-R gene is composed of two exons separated by an intron. Two GHS-R mRNA species, cGHS-R1a and cGHS-R1a-variant (cGHS-R1aV) are generated by alternative splicing of a primary transcript. cGHS-R1a protein is predicted to have seven transmembrane domains by a high degree of amino acid sequence identity with mammalian and teleost homologs. cGHS-R1aV lacks the transmembrane-6 domain due to a 48 bp deletion. RT-PCR analysis showed widespread tissue distributions of cGHS-R1a and cGHS-R1aV mRNAs with much higher amounts of cGHS-R1a in all the tissues. (C) 2003 Elsevier Inc. All rights reserved.

    DOI: 10.1016/S0016-6480(03)00247-8

    Web of Science

  • Molecular characterization of chicken growth hormone secretagogue receptor gene.

    Gen. Comp. Endocrinol.   2003年

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  • Physical exercise improves glucose metabolism in lifestyle-related diseases

    Exp. Biol. Med.   2003年

  • Physical exercise improves glucose metabolism in lifestyle-related diseases

    Exp. Biol. Med.   2003年

  • Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity

    N Nakai, M Murata, M Nagahama, T Hirase, M Tanaka, T Fujikawa, N Nakao, K Nakashima, S Kawanishi

    FREE RADICAL RESEARCH   37 ( 1 )   69 - 76   2003年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Toluene is widely used as an organic solvent in various industries and commercial products. Recent investigations have shown that toluene may induce male reproductive dysfunctions and carcinogenicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of toluene on the male reproductive system in rats, comparing to those of diethylstilbestrol (DES), a potent synthetic estrogen. Toluene (50, 500 mg/kg) or DES (2 mg/kg) injected subcutaneously to male Sprague-Dawley rats once a day for 10 days decreased the epididymal sperm counts and the serum concentrations of testosterone. The mRNA level for gonadotropin-releasing hormone receptor in the pituitary was decreased by DES, but not by toluene. On the contrary, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in testes, the biological marker for oxidative DNA damage, was increased by toluene but not by DES. These results suggest that toluene induces reproductive toxicity via direct oxidative damage of spermatozoa, whereas DES affects endocrine systems via the hypothalamo-pituitary-gonadal axis. Morphological findings supported the idea. To determine the mechanism of 8-oxodG formation in vivo , we examined DNA damage induced by toluene metabolic products in vitro . Minor toluene metabolites, methylhydroquinone and methylcatechols, induced oxidative DNA damage, and the methylcatechols induced NADH-mediated 8-oxodG formation more efficiently than methylhydroquinone did. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by toluene.

    DOI: 10.1080/1071576021000033103

    Web of Science

  • Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity

    N Nakai, M Murata, M Nagahama, T Hirase, M Tanaka, T Fujikawa, N Nakao, K Nakashima, S Kawanishi

    FREE RADICAL RESEARCH   37 ( 1 )   69 - 76   2003年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Toluene is widely used as an organic solvent in various industries and commercial products. Recent investigations have shown that toluene may induce male reproductive dysfunctions and carcinogenicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of toluene on the male reproductive system in rats, comparing to those of diethylstilbestrol (DES), a potent synthetic estrogen. Toluene (50, 500 mg/kg) or DES (2 mg/kg) injected subcutaneously to male Sprague-Dawley rats once a day for 10 days decreased the epididymal sperm counts and the serum concentrations of testosterone. The mRNA level for gonadotropin-releasing hormone receptor in the pituitary was decreased by DES, but not by toluene. On the contrary, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in testes, the biological marker for oxidative DNA damage, was increased by toluene but not by DES. These results suggest that toluene induces reproductive toxicity via direct oxidative damage of spermatozoa, whereas DES affects endocrine systems via the hypothalamo-pituitary-gonadal axis. Morphological findings supported the idea. To determine the mechanism of 8-oxodG formation in vivo , we examined DNA damage induced by toluene metabolic products in vitro . Minor toluene metabolites, methylhydroquinone and methylcatechols, induced oxidative DNA damage, and the methylcatechols induced NADH-mediated 8-oxodG formation more efficiently than methylhydroquinone did. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by toluene.

    DOI: 10.1080/1071576021000033103

    Web of Science

  • Oxidative DNA damage induced by toluene is involved in its male reproductive toxicity

    N Nakai, M Murata, M Nagahama, T Hirase, M Tanaka, T Fujikawa, N Nakao, K Nakashima, S Kawanishi

    FREE RADICAL RESEARCH   37 ( 1 )   69 - 76   2003年

     詳細を見る

    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Toluene is widely used as an organic solvent in various industries and commercial products. Recent investigations have shown that toluene may induce male reproductive dysfunctions and carcinogenicity. To clarify whether the toxicity results from the interference of endocrine systems or direct damage to reproductive organs, we examined the effects of toluene on the male reproductive system in rats, comparing to those of diethylstilbestrol (DES), a potent synthetic estrogen. Toluene (50, 500 mg/kg) or DES (2 mg/kg) injected subcutaneously to male Sprague-Dawley rats once a day for 10 days decreased the epididymal sperm counts and the serum concentrations of testosterone. The mRNA level for gonadotropin-releasing hormone receptor in the pituitary was decreased by DES, but not by toluene. On the contrary, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in testes, the biological marker for oxidative DNA damage, was increased by toluene but not by DES. These results suggest that toluene induces reproductive toxicity via direct oxidative damage of spermatozoa, whereas DES affects endocrine systems via the hypothalamo-pituitary-gonadal axis. Morphological findings supported the idea. To determine the mechanism of 8-oxodG formation in vivo , we examined DNA damage induced by toluene metabolic products in vitro . Minor toluene metabolites, methylhydroquinone and methylcatechols, induced oxidative DNA damage, and the methylcatechols induced NADH-mediated 8-oxodG formation more efficiently than methylhydroquinone did. We propose that oxidative DNA damage in the testis plays a role in reproductive toxicity induced by toluene.

    DOI: 10.1080/1071576021000033103

    Web of Science

  • Clofibric acid stimulates branched-chain amino acid catabolism by three mechanisms

    R Kobayashi, T Murakami, M Obayashi, N Nakai, J Jaskiewicz, Y Fujiwara, Y Shimomura, RA Harris

    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS   407 ( 2 )   231 - 240   2002年11月

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    記述言語:英語   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Clofibrate promotes catabolism of branched-chain amino acids by increasing the activity of the branched-chain alpha-keto acid dehydrogenase [BCKDH] complex. Depending upon the sex of the rats, nutritional state, and tissue being studied, clofibrate can affect BCKDH complex activity by three different mechanisms. First, by directly inhibiting BCKDH kinase activity, clofibrate can increase the proportion of the BCKDH complex in the active, dephosphorylated state. This occurs in situations in which the BCKDH complex is largely inactive due to phosphorylation, e.g., in the skeletal muscle of chow-fed rats or in the liver of female rats late in the light cycle. Second, by increasing the levels at which the enzyme components of the BCKDH complex are expressed, clofibrate can increase the total enzymatic activity of the BCKDH complex. This is readily demonstrated in livers of rats fed a low-protein diet, a nutritional condition that induces a decrease in the level of expression of the BCKDH complex. Third, by decreasing the amount of BCKDH kinase expressed and therefore its activity, clofibrate induces an increase in the percentage of the BCKDH complex in the active, dephosphorylated state. This occurs in the livers of rats fed a low-protein diet, a nutritional condition that causes inactivation of the BCKDH complex due to upregulation of the amount of BCKDH kinase. WY-14,643, which, like clofibric acid, is a ligand for the peroxisome-proliferator-activated receptor alpha [PPARalpha], does not directly inhibit BCKDH kinase but produces the same long-term effects as clofibrate on expression of the BCKDH complex and its kinase. Thus, clofibrate is unique in its capacity to stimulate BCAA oxidation through inhibition of BCKDH kinase activity, whereas PPARalpha activators in general promote BCAA oxidation by increasing expression of components of the BCKDH complex and decreasing expression of the BCKDH kinase. (C) 2002 Elsevier Science (USA). All rights reserved.

    DOI: 10.1016/S0003-9861(02)00472-1

    Web of Science

  • Exercise training increases the activity of pyruvate dehydrogenase complex in skeletal muscle of diabetic rats

    N Nakai, Y Miyazaki, Y Sato, Y Oshida, M Nagasaki, M Tanaka, K Nakashima, Y Shimomura

    ENDOCRINE JOURNAL   49 ( 5 )   547 - 554   2002年10月

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    記述言語:英語   出版者・発行元:JAPAN ENDOCRINE SOCIETY  

    The effects of diabetes and exercise training on the activity of pyruvate dehydrogenase (PDH) complex in skeletal muscle were examined in rats. Male Sprague-Dawley rats were divided into four groups as follows: non-diabetic sedentary, non-diabetic trained, diabetic sedentary, and diabetic trained groups. Diabetic rats were prepared by a bolus injection of intravenous streptozotocin (50 mg/kg body weight). Exercise training was performed by having rats run on a treadmill at a speed of 25 m/min for 45 min/day, 6 days/wk for 4 wks. Exercise training decreased serum concentrations of glucose and non-esterified fatty acid in diabetic rats. GLUT4 content in skeletal muscle in sedentary rats was significantly decreased by diabetes; however, exercise training significantly increased the GLUT4 content in diabetic rats. The total and actual activities and the proportion of actual activity of the PDH complex were decreased in diabetic sedentary rats. Exercise training did not affect the total activity of the PDH complex in non-diabetic rats, whereas it increased the total activity in diabetic rats to the same level as that in non-diabetic rats. In diabetic rats, exercise training tended to increase the proportion of actual activity of the PDH complex from 2.7 +/- 0.4% to 4.7 +/- 0.8%, although the proportion of actual activity in non-diabetic rats was decreased by exercise training. The present study suggests that exercise training may improve glucose metabolism in the skeletal muscle of streptozotocin-induced diabetic rats probably through the mechanisms of increasing both GLUT4 content and the activity of the PDH complex.

    DOI: 10.1507/endocrj.49.547

    Web of Science

  • Identification of a novel first exon of prolactin receptor gene expressed in the rat brain

    M Tanaka, Y Hayashida, T Iguchi, N Nakao, M Suzuki, N Nakai, K Nakashima

    ENDOCRINOLOGY   143 ( 6 )   2080 - 2084   2002年6月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    A novel first exon, E1(4), whose sequence was distinct from those of the three known first exons, E1(1), E1(2), and E1(3), of the rat PRL receptor (PRL-R) gene was identified by cDNA cloning for the 5'-end region of PRL-R mRNA expressed in the rat brain. Sequence analysis revealed the presence of two different length E14 cDNAs. The longer cDNA contained the 243-bp E14 sequence, and the shorter cDNA lacked the 139-bp sequence at the 5'-end of the longer one. Neither El. cDNA has a second exon sequence, indicating that the E14 first exon is extensively spliced to the third exon. E1(4)-containing PRL-R mRNAs were detected only in the brain by RT-PCR and ribonuclease protection assay. The longer E14 mRNA was expressed as the major PRL-R mRNA species in the brain and was greatly increased in pregnant (d 18) and lactating (d 5) rats. A genomic clone containing the El. first exon together with its 5'- and 3'-flanking regions was isolated from a rat kidney genomic library. Ribonuclease protection assay revealed that the position corresponding to the 5'-end of the shorter El. cDNA is the major transcription start point for the E1(4)exon. The 5'-flanking region of E1(4) contained a TATA box-like element 23 bp upstream of the major transcription start point. Other putative transcription factor-binding sites, such as CCAAT, Sp1, and glucocorticoid-responsive elements, were observed at further upstream regions. These results suggest that PRL-R gene expression in rat brain is controlled by the promoter for the E1(4) first exon.

    DOI: 10.1210/en.143.6.2080

    Web of Science

  • The efficacy of acetic acid for glycogen repletion in rat skeletal muscle after exercise

    T Fushimi, K Tayama, M Fukaya, K Kitakoshi, N Nakai, Y Tsukamoto, Y Sato

    INTERNATIONAL JOURNAL OF SPORTS MEDICINE   23 ( 3 )   218 - 222   2002年4月

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    記述言語:英語   出版者・発行元:GEORG THIEME VERLAG KG  

    We examined the effect of acetic acid, the main component of vinegar, on glycogen repletion by using swimming-exercised rats. Rats were trained for 7 days by swimming. After an overnight fast, they were subjected to a 2-hr swimming exercise. Immediately after-ward, they were given by gavage 2 ml of one of the following solutions: 30% glucose only or 30% glucose with 0.4% acetic acid. Rats were sacrificed by decapitation before, immediately after exercise and 2 hours after the feeding. Exercise significantly decreased soleus and gastrocnemius glycogen content, and feeding significantly increased liver, soleus and gastrocnemius glycogen content. In soleus muscle, acetate feeding significantly increased glycogen content and the ratio of glycogen synthase in the I form (means SEM: 4.04 +/- 0.41 mg/g-tissue and 47.0 +/- 0.7%, respectively) in contrast to no acetate feeding (3.04 +/- 0.29 mg/g-tissue and 38.1 +/- 3.4 %, respectively). Thus, these findings suggest that the feeding of glucose with acetic acid can more speedily accelerate glycogen repletion in skeletal muscle than can glucose only.

    DOI: 10.1055/s-2002-23172

    Web of Science

  • Exercise Training Increases the Activity of Pyruvate Dehydrogenase Complex in Skeletal Muscle of Diabetic Rats.

    Endocrine J.   2002年

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  • Exercise Training Increases the Activity of Pyruvate Dehydrogenase Complex in Skeletal Muscle of Diabetic Rats.

    Endocrine J.   49: 547-554   2002年

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  • Testis-specific and developmentally induced expression of a ghrelin gene-derived transcript that encodes a novel polypeptide in the mouse

    M Tanaka, Y Hayashida, N Nakao, N Nakai, K Nakashima

    BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION   1522 ( 1 )   62 - 65   2001年11月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Ghrelin is a novel growth hormone-releasing peptide isolated from rat stomach. In the present study, we report expression of a ghrelin gene-derived transcript (GGDT) in the mouse testis. Analysis of GGDT cDNA revealed that the 68 bp sequence at the 5'-end was unique and the remaining 252 bp sequence was identical with the sequence encoded by exons 4 and 5 of mouse ghrelin gene. The 5'-unique sequence encoded 12 amino acid residues being in-frame with the C-terminal 42 amino acid sequence of mouse ghrelin. The 54-amino-acid polypeptide encoded by GGDT contained no apparent signal peptide, sequence but possessed a nuclear localization signal-like sequence. Ghrelin mRNA was extensively expressed in the stomach, while GGDT was expressed only in the testis. The 5'-unique sequence of GGDT was identified between exons 3 and 4 of the ghrelin gene, indicating that GGDT was generated by alternative usage of the 68 bp exon as the testis-specific first exon. The GGDT expression in the testis was initiated and increased after 2 weeks of postnatal period. These results indicate that the expression of GGDT is regulated in testis-specific and developmental stage-specific manners. (C) 2001 Elsevier Science B.V. All rights reserved.

    DOI: 10.1016/S0167-4781(01)00304-9

    Web of Science

  • Modification by exercise training of activity and enzyme expression of hepatic branched-chain α-ketoacid dehydrogenase complex in streptozotocin-induced diabetic rats.

    . J. Nutri.l Sci. Vitaminol. (Tokyo)   47 ( 5 )   345 - 350   2001年10月

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    記述言語:英語  

    DOI: 10.3177/jnsv.47.345

    Web of Science

  • Organization of the mouse ghrelin gene and promoter: Occurrence of a short noncoding first exon

    M Tanaka, Y Hayashida, T Iguchi, N Nakao, N Nakai, K Nakashima

    ENDOCRINOLOGY   142 ( 8 )   3697 - 3700   2001年8月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Ghrelin is a growth hormone-releasing peptide recently discovered in the stomach of rat and human as an endogenous ligand for growth hormone-secretagogue receptor. In the present study, a full-length cDNA for mouse ghrelin has been cloned from the stomach using the oligo-capping and rapid amplification methods, and the organization of its gene and promoter has been analyzed. The mouse ghrelin cDNA was 521 bp long, consisting of 44 bp 5'-noncoding region, 354 bp coding region encoding a pre-proghrelin composed of 117 amino acid residues and 123 bp 3'-noncoding region. The genomic sequence analysis has revealed that the mouse ghrelin gene consists of 5 exons and 4 introns. The first exon was revealed to be only 19 bp long presented at the noncoding region of cDNA. The identical 19 bp sequence was also found as the first exon at the 5'-end of full-length rat ghrelin cDNA obtained from the stomach. A TATA box-like sequence, TATATAA was localized 24 bp upstream of the transcription start site of the mouse ghrelin gene. The sequence of the 5'-promoter region of mouse ghrelin gene including the TATA-like sequence and short exon I was highly homologous to that of reported human ghrelin gene. These findings suggest that the structure of the promoter region including the short noncoding first exon and its transcriptional regulation are conserved among the mammalian ghrelin genes.

    DOI: 10.1210/en.142.8.3697

    Web of Science

  • Acetic acid feeding enhances glycogen repletion in liver and skeletal muscle of rats

    T Fushimi, K Tayama, M Fukaya, K Kitakoshi, N Nakai, Y Tsukamoto, Y Sato

    JOURNAL OF NUTRITION   131 ( 7 )   1973 - 1977   2001年7月

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    記述言語:英語   出版者・発行元:AMER INST NUTRITION  

    To investigate the efficacy of the ingestion of vinegar in aiding recovery from fatigue, we examined the effect of dietary acetic acid, the main component of vinegar, on glycogen repletion in rats. Rats were allowed access to a commercial diet twice daily for 6 d. After 15 h of food deprivation, they were either killed immediately or given 2 g of a diet containing 0 (control), 0.1, 0.2 or 0.4 g acetic acid/100 g diet for 2 h. The 0.2 g acetic acid group had significantly greater liver and gastrocnemius muscle glycogen concentration than the control group (P &lt; 0.05). The concentrations of citrate in this group in both the liver and skeletal muscles were &gt;1.3-fold greater than in the control group (P &gt; 0.1). In liver, the concentration of xylulose-5-phosphate in the control group was significantly higher than in the 0.2 and 0.4 g acetic acid groups (P &lt; 0.01). In gastrocnemius muscle, the concentration of glucose-6-phosphate in the control group was significantly lower and the ratio of fructose-1,6-bisphosphate/fructose-6-phosphate was significantly higher than in the 0.2 g acetic acid group (P &lt; 0.05). This ratio in the soleus muscle of the acetic acid fed groups was &lt;0.8-fold that of the control group (P &gt; 0.1). In liver, acetic acid may activate gluconeogenesis and inactivate glycolysis through inactivation of fructose-2, 6-bisphosphate synthesis due to suppression of xylulose-5-phosphate accumulation. In skeletal muscle, acetic acid may inhibit glycolysis by suppression of phosphofructokinase-1 activity. We conclude that a diet containing acetic acid may enhance glycogen repletion in liver and skeletal muscle.

    DOI: 10.1093/jn/131.7.1973

    Web of Science

  • Effects of troglitazone and voluntary running on insulin resistance induced high fat diet in the rat

    K Kitakoshi, Y Oshida, N Nakai, YQ Han, Y Sato

    HORMONE AND METABOLIC RESEARCH   33 ( 6 )   365 - 369   2001年6月

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    記述言語:英語   出版者・発行元:GEORG THIEME VERLAG KG  

    It is well known that troglitazone and voluntary running have the rapacity to improve insulin resistance. The purpose of this study was to evaluate the combination effect of troglitazone and voluntary running on insulin action. Female rats aged 7 weeks were divided into high-fat diet (HF), high-fat diet + troglitazone (0.3% in diet; Tg), high-fat diet + voluntary running (for 3 wks: Tr), high-fat diet + troglitazone + voluntary running (Tg-Tr), and control (C) groups. A sequential euglycemic clamp experiment with two different insulin infusion rates of 3.0 IL-clamp) and 30.0 mU/kg BW/min (H-clamp) was performed on these rats after an overnight fast. Blood glucose concentrations were kept at fasting levels by periodic adjustment of the intravenous glucose infusion rate during the clamp experiment. Glucose infusion rates (GIRs) calculated from 60 to 90, 150 to 180 min were regarded as an index of whole body insulin action. After the clamp experiment, we determined the amount of glycogen content in the gastrocnemius muscle. Fat feeding markedly reduced GIRs in both L- and H- clamp experiments compared with C. Troglitazone treatment did not improve high-fat induced insulin resistance. In both L- and H-clamp experiments, GIRs were increased by voluntary running compared with HF, and reached the same levels as in C. GIRs of Tg-Tr were not greater than those of Tr. Glycogen content in gastrocnemius muscle showed the same trend as the results for GIRs. Therefore, the combination effect of troglitazone and voluntary running on insulin action was not found, but the effect of voluntary running was shown in fat-induced insulin resistance.

    DOI: 10.1055/s-2001-15412

    Web of Science

  • The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats

    N Nakai, M Obayashi, M Nagasaki, Y Sato, N Fujitsuka, A Yoshimura, Y Miyazaki, S Sugiyama, Y Shimomura

    LIFE SCIENCES   68 ( 5 )   497 - 503   2000年12月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The abundance of mRNAs for pyruvate dehydrogenase kinase (PDK) isoenzymes in four brain regions of young (10 wk) and aged (50 wk) rats was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNAs for PDK1,2, and 4 were detected in all the regions examined, The level of PDK2 mRNA was the most abundant among the isoenzymes in all the brain regions when judged from the PCR cycles. The level of PDK1 mRNA was relatively high in cerebellum and cerebral cortex compared to medulla oblongata and hippocampus. Aging decreased the levels of mRNAs for PDK1 and 2 in cerebellum and increased the PDK2 mRNA in hippocampus and cerebral cortex. The level of PDK4 mRNA was not affected by aging. These results provide the first evidence suggesting that there is the regional difference in the abundance of mRNAs for PDK isoenzymes in rat brain and that the levels of mRNAs for the isoenzymes were affected by aging. (C) 2000 Elsevier Science Inc. All rights reserved.

    DOI: 10.1016/S0024-3205(00)00947-4

    Web of Science

  • The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats

    N Nakai, M Obayashi, M Nagasaki, Y Sato, N Fujitsuka, A Yoshimura, Y Miyazaki, S Sugiyama, Y Shimomura

    LIFE SCIENCES   68 ( 5 )   497 - 503   2000年12月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The abundance of mRNAs for pyruvate dehydrogenase kinase (PDK) isoenzymes in four brain regions of young (10 wk) and aged (50 wk) rats was investigated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNAs for PDK1,2, and 4 were detected in all the regions examined, The level of PDK2 mRNA was the most abundant among the isoenzymes in all the brain regions when judged from the PCR cycles. The level of PDK1 mRNA was relatively high in cerebellum and cerebral cortex compared to medulla oblongata and hippocampus. Aging decreased the levels of mRNAs for PDK1 and 2 in cerebellum and increased the PDK2 mRNA in hippocampus and cerebral cortex. The level of PDK4 mRNA was not affected by aging. These results provide the first evidence suggesting that there is the regional difference in the abundance of mRNAs for PDK isoenzymes in rat brain and that the levels of mRNAs for the isoenzymes were affected by aging. (C) 2000 Elsevier Science Inc. All rights reserved.

    DOI: 10.1016/S0024-3205(00)00947-4

    Web of Science

  • The α-ketoisocaproate catabolism in human and rat livers.

    Biochem. Biophys. Res. Commun.   276 ( 3 )   1080 - 1084   2000年10月

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    記述言語:英語  

    DOI: 10.1006/bbrc.2000.3566

    Web of Science

  • Exercise training prevents maturation-induced decreases in insulin receptor substrate-1 and phosphatidylinositol 3-kinase in rat skeletal muscle

    M Nagasaki, N Nakai, Y Oshida, ZH Li, M Xu, M Obayashi, T Murakami, A Yoshimura, N Fujitsuka, Y Shimomura, Y Sato

    METABOLISM-CLINICAL AND EXPERIMENTAL   49 ( 7 )   954 - 958   2000年7月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO  

    We have previously reported that exercise training prevents a maturation-induced decrease in insulin sensitivity and suggested that an improvement of insulin sensitivity by exercise training was attributable, in part, to an increase in insulin-sensitive GLUT-4 on the skeletal muscle plasma membrane. In this study, we examined the effects of maturation and exercise training on the gene expression and protein content of the components of post-insulin receptor signal transduction in rat skeletal muscle. Rats aged 3 weeks were sedentary or trained by voluntary running through 4 or 27 weeks of age, and then the rats in both the sedentary and trained groups were kilted and the gastrocnemius muscle was immediately removed for analysis of mRNA and protein content. The concentration of mRNA and protein for insulin receptor substrate-1 (IRS-1) in sedentary rats significantly decreased with maturation (49% and 63%, respectively, at age 27 weeks v age 4 weeks), but in trained rats they did not decrease with maturation. Although the level of phosphatidylinositol 3-kinase (PI 3-kinase) mRNA in sedentary rats was not altered with maturation, PI 3-kinase protein in sedentary rats significantly decreased with maturation (73% at 27 weeks v 4 weeks). However, PI 3-kinase protein in trained rats did not decrease with maturation. These results suggest that the prevention of maturation-induced decreases in the protein content of IRS-1 and PI 3-kinase is involved in the mechanisms responsible for the improvement of insulin sensitivity by exercise training, and exercise training may affect transcriptional regulation of the IRS-1 gene and posttranscriptional regulation of PI 3-kinase expression. Copyright (C) 2000 by W.B. Saunders Company.

    DOI: 10.1053/meta.2000.6758

    Web of Science

  • Additive effects of estrogen deficiency and diabetes on bone mineral density in rats

    M Fukuharu, J Sato, Ohsawa, I, Y Oshida, M Nagasaki, N Nakai, Y Shimomura, M Hattori, S Tokudome, Y Sato

    DIABETES RESEARCH AND CLINICAL PRACTICE   48 ( 1 )   1 - 8   2000年4月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    We investigated the combined effects of estrogen deficiency and diabetes on bone mineral density (BMD) and bone metabolism in rats. Ten-week-old, female rats were randomly divided into four groups: controls (C), an ovariectomized group (O), a streptozotocin-induced diabetic group (S), and a combined ovariectomy and streptozotocin-induced diabetic group (OS). The BMD of the lumbar spine and the femur were measured before grouping and at 23 weeks old. At the end of the experiment, blood samples were obtained via cardiac puncture, and bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP) and 1,25-dihydroxyvitamin D levels were measured. The rats in the C, O, S, and OS groups, in that order, had higher levels of BMD of the lumbar spine and femur at 23 weeks of age. The BGP levels in the S and OS groups were significantly lower than in C and O groups. Significantly higher 1,25-dihydroxyvitamin D was observed in the O group compared with the C, S and OS groups. No differences were obtained in TRAP among four groups. Our data suggest that the combined effects of estrogen deficiency and diabetes on BMD are not synergistic or counteractive but additive. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0168-8227(99)00141-2

    Web of Science

  • Suppression of glycogen consumption during acute exercise by dietary branched-chain amino acids in rats

    Y Shimomura, T Murakami, N Nakai, M Nagasaki, M Obayashi, ZH Li, M Xu, Y Sato, T Kato, N Shimomura, N Fujitsuka, K Tanaka, M Sato

    JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY   46 ( 2 )   71 - 77   2000年4月

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    記述言語:英語   出版者・発行元:CENTER ACADEMIC PUBL JAPAN  

    The effects of a diet supplemented with branched-chain amino acids (BCAA; 4.8% or 6.2%) on BCAA catabolism and glycogen metabolism in rats were examined. Rats were fed a BCAA diet or control diet for 4 wk and part of the rats were subjected to exercise training during the experimental period. Feeding the BCAA diet increased serum BCAA concentrations and activity of the hepatic branched-chain alpha-keto acid dehydrogenase complex, the rate-limiting enzyme in the catabolism of BCAA, suggesting that dietary BCAA promotes BCAA catabolism. Although the serum glucose concentration and glycogen contents in the liver and gastrocnemius muscle of rested rats were not significantly affected by feeding of the BCAA diet, those in rats exhausted by acute exercise were 2-4-fold higher in rats fed the BCAA diet than in rats fed the control diet. The activity of pyruvate dehydrogenase complex in the liver and gastrocnemius muscle after acute exercise showed reverse trends; the complex activities (especially in liver) tended to be less in the BCAA diet group than in the control diet group. These results suggest that dietary BCAA spares glycogen stores in liver and skeletal muscle during exercise and that the decrease in pyruvate dehydrogenase complex activity in these tissues by dietary BCAA is involved in the mechanisms.

    DOI: 10.3177/jnsv.46.71

    Web of Science

  • Alpha-ketoisocaproate dioxygenase in rat and human livers

    M Xu, N Nakai, M Nagasaki, Y Sato, N Fujitsuka, Y Shimomura

    FASEB JOURNAL   14 ( 4 )   A746 - A746   2000年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • The abundance of mRNAs for pyruvate dehydrogenase kinase isoenzymes in brain regions of young and aged rats.

    Life Sci.   2000年

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  • Determination of branched-chainα-keto acid dehydrogenase activity state in mammals.

    Methods Enzymol.   324: 48-62   2000年

  • Exercise, Nutrition and Environmental Stress

    2000年

  • Purification of 3-hydroxyisobutyryl-CoA hydrolase.

    Methods Enzymol.   324: 229-240   2000年

  • Expression of mRNAs for c-myc and branched-chain aminotransferases in human gastric cancer cells and tissues

    T Kato, H Goto, Y Niwa, N Ohmiya, T Hayakawa, T Murakami, N Nakai, SM Hutson, Y Shimomura

    JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION   29   29 - 36   2000年

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    記述言語:英語   出版者・発行元:JOURNAL CLINICAL BIOCHEMISTRY & NUTRITION  

    It has been established that there are two isoforms of mammalian branched-chain aminotransferases, cytosolic (BCATc) and mitochondrial (BCATm). Since the BCATc was reported to be a direct target for c-Myc regulation, we investigated expression of mRNAs for c-myc, BCATc, and BCATm in human gastric cancer cells and tissues. MKN45 and KATOIII were used as human gastric cancer cell lines. Human gastric mucosal tissues with cancer were obtained from 9 patients and those with non-ulcer dyspepsia (NUD) were from 8 patients by endoscopic biopsy. Expression of mRNA was measured by the method of polymerase-chain reaction coupled with reverse transcription. Expression of c-myc mRNA was detected in both cell lines but was greater in MKN45. Expression of BCATc mRNA was detected in KATOIII, but not in MKN45, whereas expression of BCATm mRNA was detected only in MKN45. In the analyses of human gastric tissues, it was found that c-myc mRNA was expressed in all of the tissues examined, but overexpression of the mRNA was detected in the 5 tissues with cancer. On the other hand, expression of BCATc mRNA was detected in 4 tissues with gastric cancer, in which only one tissue had the overexpression of c-myc mRNA. Expression of BCATc mRNA was not detected in all tissues with NUD. BCATm mRNA expression was detected in all tissues with cancer or NUD. These results suggest that there is no correlation between expression of mRNAs for c-myc and BCATc in these tissues and that expression of BCATc in gastric cancer cells and tissues is regulated in a manner independent of c-myc expression.

    DOI: 10.3164/jcbn.29.29

    Web of Science

  • Exercise, Nutrition and Environmental Stress

    Cooper Publishing Group, LLC   2000年

  • Effects of aging and exercise training on insulin receptor, IRS-1 and PI 3-kinase in rat skeletal muscle.

    M Nagasaki, N Nakai, Y Shimomura, T Murakami, N Fujitsuka, Y Oshida, Y Sato

    FASEB JOURNAL   13 ( 5 )   A1054 - A1054   1999年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effects of ovariectomy and sex steroid treatment on hepatic branched-chain alpha-keto acid dehydrogenase complex (BCKDC) activity in female rats.

    M Obayashi, N Nakai, Y Shimomura, T Murakami, N Fujitsuka, Y Oshida, Y Sato

    FASEB JOURNAL   13 ( 4 )   A234 - A234   1999年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effects of diabetes and exercise training on the activity of branched-chain alpha-keto acid dehydrogenase complex (BCKDC) in rat liver.

    Z Li, T Murakami, N Nakai, Y Shimomura, N Fujitsuka, Y Oshida, Y Sato

    FASEB JOURNAL   13 ( 4 )   A567 - A567   1999年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Hepatic branched-chain a-keto acid dehydrogenase complex in female rats: activation by exercise and starvation

    Rumi Kobayashi, Yoshiharu Shimomura, Taro Murakami, Naoya Nakai, Megumi Otsuka, Nobuhiko Arakawa, Kazuyuki Shimizu, Robert A. Harris

    Journal of Nutritional Science and Vitaminology   45 ( 3 )   303 - 309   1999年1月

     詳細を見る

    The effects of acute exercise and starvation on hepatic branched-chain α-keto acid dehydrogenase (BCKDH) complex activity were examined in female rats fed high (30%)- or low (8%)-protein diets. The total activity of the complex was significantly higher in the high protein-fed rats than in the low protein-fed rats but was not affected by acute exercise and starvation in either diet group. The proportion of the active form of BCKDH complex was less than 10% in both diet groups. Acute exercise and starvation markedly increased the active form of the complex in both diet groups. The activity of BCKDH kinase, which is responsible for inactivation of the BCKDH complex by phosphorylation, tended to be decreased by acute exercise and starvation in both diet groups. These results suggest that the activity of the BCKDH kinase is an important factor determining the proportion of the active form of BCKDH complex in exercise and starvation, and that the female rat is a useful model for studying the regulation of hepatic BCKDH complex activity.

    DOI: 10.3177/jnsv.45.303

    Scopus

    PubMed

  • 317.トレーニングラットの分岐鎖アミノ酸(BCAA)及びグリコーゲン代謝に対するBCAA添加食の影響

    下村 吉治, 村上 太郎, 中井 直也, 長崎 大, 李 志浩, 徐 明, 尾林 麻里子, 佐藤 祐造, 下村 典子, 佐藤 学, 田中 和永

    体力科學   47 ( 6 )   861 - 861   1998年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • 388.運動トレーニングが糖尿病ラット肝臓の分岐鎖α-ケト酸脱水素酵素復合体活性におよぼす影響

    李 志浩, 下村 吉治, 村上 太郎, 中井 直也, 押田 芳治, 佐藤 祐造

    体力科學   47 ( 6 )   896 - 896   1998年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • Branched-chain α-keto acid dehydrogenase kinase content in rat skeletal muscle is decreased by endurance training

    Hisao Fujii, Yoshiharu Shimomura, Taro Murakami, Naoya Nakai, Tasuku Sato, Masashige Suzuki, Robert A. Harris

    Biochemistry and Molecular Biology International   44 ( 6 )   1211 - 1216   1998年1月

     詳細を見る

    The activity state of branched-chain α-keto acid dehydrogenase complex in skeletal muscle was elevated by running exercise in trained and untrained rats, but level of this elevation was significantly greater in the former than in the latter. To elucidate the mechanism of the training effect on the exercise-induced activation of the complex, a protein amount of branched chain α-keto acid dehydrogenase kinase, which is responsible for inactivation of the complex by phosphorylation, in the muscle was measured by the Western blot analysis. Endurance training decreased the content of the kinase protein in the muscle by ~30%, suggesting that this decrease is involved in the mechanisms for greater activation of the complex by exercise in trained rats.

    DOI: 10.1080/15216549800202302

    Scopus

    PubMed

  • 231.分岐鎖アミノ酸代謝に及ぼす食餌タンパク質と運動トレーニングの影響

    下村 吉治, 村上 太郎, 藤墳 規明, 中井 直也, 下村 典子

    体力科學   46 ( 6 )   728 - 728   1997年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • Gender difference in regulation of branched-chain amino acid catabolism

    Rumi Kobayashi, Yoshiharu Shimomura, Taro Murakami, Naoya Nakai, Noriaki Fujitsuka, Megumi Otsuka, Nobuhiko Arakawa, Kirill M. Popov, Robert A. Harris

    Biochemical Journal   327 ( 2 )   449 - 453   1997年10月

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    Regulation of the activity state of the hepatic branched-chain 2-oxo acid dehydrogenase (BCODH) complex during the light-dark cycle differs markedly in male and female rats. Female rats exhibit a profound diurnal rhythm in the activity state of the complex that is not observed in male rats. Regardless of gender, most of the complex was dephosphorylated and active in the middle of the dark period and early in the light period, and this form of the complex predominated in male rats at the end of the light period. In contrast, most of the complex in female rats became phosphorylated and inactive by the end of the light period. Gonadectomy prevented the diurnal rhythm in females but was without effect in males, indicating that female sex hormones are required for this gender difference in regulation of the BCODH complex. Changes in levels of branched-chain 2-oxo acids, known regulators of BCODH kinase, do not seem to be involved; rather, an increase in BCODH kinase activity occurring between morning and evening is responsible for inactivation of the BCODH complex in female rats. The increase in kinase activity is due to an increase in the amount of kinase protein associated with the BCODH complex. Thus a marked diurnal variation in the amount of BCODH kinase and therefore its activity results in large swings in the activity state of the liver BCODH complex in female rats. This study provides the first evidence for a gender-specific difference in the regulation of branched-chain amino acid catabolism.

    DOI: 10.1042/bj3270449

    Scopus

    PubMed

  • 19.ラット血清分岐鎖アミノ酸濃度へ及ぼす食餌タンパク質と運動トレーニングの影響(第1回日本体力医学会東海地方会)

    下村 吉治, 村上 太郎, 藤墳 規明, 中井 直也

    体力科學   46 ( 5 )   544 - 544   1997年10月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • The activity of branched-chain α-keto acid dehydrogenase complex in rat digestive tracts: Effects of dietary protein and exercise

    Midoriko Tsukamura, Hidemi Goto, Tomiyasu Arisawa, Tetsuo Hayakawa, Rumi Kobayashi, Naoya Nakai, Taro Murakami, Satoru Sugiyama, Yoshiharu Shimomura

    Biochemistry and Molecular Biology International   42 ( 4 )   717 - 722   1997年7月

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    Branched-chain α-keto acid dehydrogenase complex is the rate limiting enzyme in catabolism of branched-chain amino acids. In this study, we examined effects of dietary protein and exercise on the complex activity in digestive tracts (stomach, small intestine and colon) of rats. Rats were fed a high (30%) or low (8%) protein diet for 3 weeks and a half of rats in each diet group was exercised by 85 min running just prior to sacrifice on the final day of the experiment. Total and actual (active form) activities of the complex were markedly high in stomach compared to other two tissues and the actual activity in stomach was significantly elevated by exercise only in rats fed the high protein diet. Both total and actual activities in colon were only a few percentage of those in stomach, and those in small intestine was further less. These results suggest that rat stomach is the tissue active in catabolism of branched-chain amino acids, which is promoted by combination of high protein diet and exercise.

    DOI: 10.1080/15216549700203141

    Scopus

  • Effects of aging and starvation on the activities of pyruvate dehydrogenase complex and its kinase in rat heart.

    N Nakai, Y Sato, Y Oshida, N Fujitsuka, Y Shimomura

    FASEB JOURNAL   11 ( 3 )   2930 - 2930   1997年2月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • 520.女性ホルモンによる分岐鎖アミノ酸代謝の調節 : 分岐鎖α-ケト酸脱水素酵素複合体活性の調節

    下村 吉治, 村上 太郎, 中井 直也

    体力科學   45 ( 6 )   864 - 864   1996年12月

     詳細を見る

    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • Activity of liver pyruvate dehydrogenase complex in Psammomys obesus

    N Nakai, Y Shimomura, N Fujitsuka, Y Sato, GR Collier

    FASEB JOURNAL   10 ( 3 )   4306 - 4306   1996年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Effects of dietary protein and exercise on the activity of branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) in rat digestive tract.

    M Tsukamura, H Goto, T Arisawa, T Hayakawa, R Kobayashi, T Murakami, N Nakai, N Fujitsuka, Y Shimomura

    FASEB JOURNAL   10 ( 3 )   4265 - 4265   1996年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Sex differences in activities of branched-chain alpha-keto acid dehydrogenase (BCKDH) complex and BCKDH kinase in rat livers.

    R Kobayashi, T Murakami, N Nakai, M Otsuka, N Arakawa, RA Harris, Y Shimomura

    FASEB JOURNAL   10 ( 3 )   4267 - 4267   1996年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Ron Manghan's Biochemistry of Exercise IX

    Human Kinetics, Illinois, USA   1996年

  • Ron Manghan’s Biochemistry of Exercise IX

    Human Kinetics, Illinois, USA   1996年

  • 503.雌ラット肝臓の分岐鎖アミノ酸代謝に対する食餌タンパクと運動の影響

    下村 吉治, 中井 直也, 村上 太郎, 藤墳 規明

    体力科學   44 ( 6 )   858 - 858   1995年12月

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    記述言語:日本語   出版者・発行元:日本体力医学会  

    CiNii Books

  • EFFECTS OF PHYSICAL-TRAINING AND AGING ON INSULIN ACTION AND GLUT-4 CONTENT IN MUSCLE PLASMA-MEMBRANE

    Y SATO, Y OSHIDA, N NAKAI, N OHSAKI, J SATO, Y SHIMOMURA

    DIABETOLOGIA   38   A179 - A179   1995年8月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:SPRINGER VERLAG  

    Web of Science

  • EFFECTS OF DIETARY-PROTEIN AND EXERCISE ON THE ACTIVITY OF BRANCHED-CHAIN ALPHA-KETOACID DEHYDROGENASE COMPLEX (BCKDC)

    R KOBAYASHI, T MURAKAMI, N NAKAI, M OTSUKA, N ARAKAWA, RA HARRIS, Y SHIMOMURA

    FASEB JOURNAL   9 ( 4 )   A743 - A743   1995年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • HIGH-SALT DIET INCREASES PYRUVATE-DEHYDROGENASE (PDH) KINASE-ACTIVITY AND DECREASES PDH COMPLEX ACTIVITY IN DIABETIC RAT-HEART

    N NAKAI, Y SATO, N FUJITSUKA, RA HARRIS, Y SHIMOMURA

    FASEB JOURNAL   9 ( 4 )   A750 - A750   1995年3月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

  • Regulation by physical training of enzyme activity and gene expression of branched-chain 2-oxo acid dehydrogenase complex in ratskeletal muscle

    Hisao Fujii, Kumpei Tokuyama, Masashige Suzuki, Kirill M. Popov, Yu Zhao, Robert A. Harris, Naoya Nakai, Taro Murakami, Yoshiharu Shimomura

    Biochim. Biophys. Acta   1243 ( 2 )   277 - 281   1995年2月

     詳細を見る

    We examined the effects of short-term (5 weeks) and long-term (12 weeks) physical training on actual and total activities, protein content and mRNA abundance of branched-chain 2-oxo acid dehydrogenase complex in rat skeletal muscle. The actual and total activities were significantly increased ∼ 60% and ∼ 40%, respectively, by long term training. No effects of short-term training on activities were observed. The increase in the total activity corresponded to increased protein content of the E1α and E2 components of the complex. On the other hand, mRNA abundance for E1α and E2 were not affected by the training, but that for E1β was slightly, but significantly increased by both short-term and long-term trainings. These divergent alterations of the message levels for the subunits of the complex suggest that posttranslational regulatory mechanisms determine the amount of the complex in skeletal muscle. Since the complex is located in the mitochondrial matrix space, mitochondrial biogenesis in response to the training was examined by determining the content of mitochondrial DNA in the muscle. The mitochondrial DNA was proportionally increased with the total activity as well as the protein content of the complex, suggesting that expression of branched-chain 2-oxo acid dehydrogenase complex in skeletal muscle in response to physical training is associated with mitochondrial biogenesis. © 1995.

    DOI: 10.1016/0304-4165(94)00149-R

    Scopus

    PubMed

  • Branched-chain α-keto acid dehydrogenase complex in rat skeletal muscle: Regulation of the activity and gene expression by nutrition and physical exercise

    Y. Shimomura, H. Fujii, M. Suzuki, T. Murakami, N. Fujitsuka, N. Nakai

    Journal of Nutrition   125 ( 6 SUPPL. )   1995年1月

     詳細を見る

    Branched-chain α-keto acid dehydrogenase complex is the rate-limiting enzyme in the catabolism of branched-chain amino acids in skeletal muscle. It is suggested that activation of this enzyme in the muscle during exercise plays an important role in the increased oxidation of branched-chain amino acids in the muscle. Evidence suggests that branched-chain α-keto acids, the substrates for the enzyme, regulate the activity state of the enzyme in the muscle during exercise through phosphorylation/dephosphorylation cycle of the enzyme protein. We propose a model for the mechanism of enzyme activation by exercise. In addition to this acute effect of exercise, we present evidence suggesting that exercise training modulates the enzyme activity and gene expression for the enzyme. Increases in the total activity as well as enzyme proteins by exercise training are suggested to be associated with mitochondrial biogenesis in the muscle.

    Scopus

    PubMed

  • Diabetes 1994

    Elsevier Science B. V.   1995年

  • Diabetes 1994

    Elsevier Science B. V.   1995年

  • Glucose fluxes, exercise and diabetes

    Smith-Gordon and Company Ltd.   1995年

  • Glucose fluxes, exercise and diabetes

    Smith-Gordon and Company Ltd.   1995年

  • Purification and partial characterization of 3-hydroxyisobutyryl-coenzyme A hydrolase of rat liver.

    Yoshiharu Shimomura, Yoshiharu Shimomura, Taro Murakami, Noriaki Fujitsuka, Naoya Nakai, Yuzo Sato, Satoru Sugiyama, Noriko Shimomura, Jamie Irwin, John W. Hawes, Robert A. Harris

    Journal of Biological Chemistry   269 ( 19 )   14248 - 14253   1994年5月

     詳細を見る

    An unusual feature of valine catabolism is a reaction in which an intermediate of its catabolic pathway, (S)-3-hydroxyisobutyryl-CoA, is hydrolyzed to give the free acid and CoA-SH. The enzyme responsible for this reaction, 3-hydroxyisobutyryl-CoA hydrolase (EC 3.1.2.4), was purified 7200- fold from rat liver in this study. The purified enzyme consists of a single polypeptide with an M(r) of 36,000 in the native and denatured forms. The hydrolase is highly specific for (S)-3-hydroxyisobutyryl-CoA and 3- hydroxypropionyl-CoA (K(m), 6 and 25 μM, respectively) with optimal activity around pH 8. The turnover rate of the enzyme for (S)-3-hydroxyisobutyryl-CoA is 270 s-1, which is high relative to other enzymes of the valine pathway. Likewise, activity of the enzyme expressed on a wet weight basis is also very high in the major tissues of the rat. These findings suggest that rapid destruction of (S)-3-hydroxyisobutyryl-CoA produced during valine catabolism is physiologically important. We propose that the need for a mechanism to protect cells against the toxic effects of methacrylyl-CoA, which is maintained in equilibrium with (S)-3-hydroxyisobutyryl-CoA by crotonase, explains why valine catabolism involves this enzyme and why its tissue activity is so high.

    Scopus

    PubMed

  • ENZYMES OF THE VALINE CATABOLIC PATHWAY IN RAT, DOG AND HUMAN TISSUES - ACTIVITIES OF METHACRYLYL-COA HYDRATASE (CROTONASE) AND 3-HYDROXYISOBUTYRYL-COA HYDROLASE

    Y SHIMOMURA, T MURAKAMI, N FUJITSUKA, N NAKAI, T OOIWA, H GOTO, T NONAMI, S SUGIYAMA, J IRWIN, JW HAWES, RA HARRIS

    FASEB JOURNAL   8 ( 7 )   A1414 - A1414   1994年4月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    Web of Science

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    研究課題/領域番号:25350813  2013年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    中井 直也

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    細胞におけるタンパク質合成はmTORとAMPKによって拮抗的に調節されているとされている。本研究では、骨格筋培養細胞を対象として、伸展刺激によるメカニカルストレスと低エネルギーストレスがmTOR/p70S6K経路とAMPK経路に及ぼす影響を検討した。伸展刺激によるメカニカルストレスはmTOR経路とAMPK経路をともに活性化し、ある種の生理的刺激下では両者の拮抗的調節は行われていないことが認められた。しかし、薬理的なAMPK活性の調節はメカニカルストレスによるmTOR経路の活性化に影響を及ぼすことが明らかとなった。

講演・口頭発表等

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    日本生化学会大会  2023年11月 

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    開催年月日: 2023年10月 - 2023年11月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:福岡  

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    中井直也、吉井梨花子、東田一彦

    日本栄養・食糧学会大会  2023年5月 

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    開催年月日: 2023年5月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:北海道  

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    日本体力医学会大会  2022年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • グルコースが筋サテライト細胞の収縮によるタンパク質合成促進シグナル活性化に及ぼす影響

    石﨑和眞、高野あぐり、東田一彦、中井直也

    日本体力医学会大会  2022年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • 絶食適応後の栄養素再補充が骨格筋タンパク質合成に及ぼす影響

    吉井梨花子、東田一彦、中井直也

    日本体力医学会大会  2022年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • 絶食後の栄養素の再補充が骨格筋タンパク質合成に及ぼす影響

    吉井 梨花子、東田一彦、中井直也

    日本栄養・食糧学会大会  2022年6月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • ミトコンドリアダイナミクスが脂肪分解に与える影響

    竹内のどか、東田一彦、中井直也

    日本生理学会大会  2022年3月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • ミトコンドリアダイナミクスが脂肪分解に与える影響

    竹内のどか, 東田一彦, 中井直也

    日本生理学会大会  2022年3月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • グルコース飢餓後のα-ケトグルタル酸添加は骨格筋細胞のタンパク質合成シグナルを活性化する

    中井直也、竹内のどか、吉井梨花子、東田一彦

    日本体力医学会大会  2021年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • 鉄欠乏は筋収縮による骨格筋タンパク質合成を低下させる

    東田一彦、竹内のどか、阿藤聡、小笠原理紀、中井直也

    日本体力医学会大会  2021年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

  • グルコース飢餓後のα-ケトグルタル酸添加は骨格筋細胞のタンパク質合成シグナルを活性化する

    中井直也, 竹内のどか, 吉井梨花子, 東田一彦

    日本体力医学会大会  2021年9月 

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    記述言語:日本語   会議種別:口頭発表(一般)  

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